Autosomal Recessive Nonsyndromic Hearing Loss

Locus (OMIM)Gene (OMIM)Key Locus References (PubMed)Key Gene References (PubMed)
Evidence (ClinGen)
DFNB1AGJB2Guilford et al., 1994; Scott et al., 1995Kelsell et al., 1997Definitive
DFNB1BGJB6del Castillo et al., 2002; Pallares-Ruiz et al., 2002Wilch et al., 2010; Abou Tayoun et al., 2016Refuted
DFNB2MYO7AGuilford et al., 1994Liu et al., 1997; Weil et al., 1997not reviewed
DFNB3MYO15AFriedman et al., 1995; Liang et al., 1998Wang et al., 1998Definitive
DFNB4SLC26A4Baldwin et al., 1995; Everett et al., 1997Everett et al., 1997Definitive
DFNB5unknownFukushima et al., 1995n/an/a
DFNB6TMIEFukushima et al., 1995Naz et al., 2002Definitive
DFNB7/11TMC1Jain et al., 1995; Scott et al., 1996Kurima et al., 2002Definitive
DFNB8/10TMPRSS3Veske et al., 1996; Bonné-Tamir et al., 1996; Berry et al., 2000Scott et al., 2001Definitive
DFNB9OTOFChaïb et al., 1996Yasunaga et al., 1999Definitive
DFNB12CDH23Chaïb et al., 1996Bork et al., 2001Definitive
DFNB13unknownMustapha et al., 1998; Masmoudi et al., 2004n/an/a
DFNB14unknownMustapha et al., 1998n/an/a
DFNB15/72/95GIPC3 (see note 1)Chen et al., 1997; Ain et al., 2007Charizopoulou et al., 2011Charizopoulou et al., 2011Rehman et al., 2011Definitive
DFNB16STRC (see note 2)Campbell et al., 1997; Villamar et al., 1999Verpy et al., 2001Definitive
DFNB17unknownGreinwald et al., 1998; Guo et al., 2004n/an/a
DFNB18AUSH1CJain et al., 1998Verpy et al., 2000Limited
DFNB18BOTOGScharders et al., 2012Schraders et al., 2012Definitive
DFNB20unknownMoynihan et al., 1999n/an/a
DFNB21TECTAMustapha et al., 1999Mustapha et al., 1999Definitive
DFNB22OTOAZwaenepoel et al., 2002Zwaenepoel et al., 2002Definitive
DFNB23PCDH15Ahmed et al., 2003Ahmed et al., 2003Limited
DFNB24RDXKhan et al., 2007Khan et al., 2007Definitive
DFNB25GRXCR1Schraders et al., 2010Schraders et al., 2010Definitive
DFNB26 (see note 3)GAB1Riazuddin et al., 2000Yousaf et al., 2018not reviewed
DFNB27unknownPulleyn et al., 2000n/an/a
DFNB28TRIOBPWalsh et al., 2000Shahin et al., 2006; Riazuddin et al., 2006Definitive
DFNB29CLDN14Wilcox et al., 2001Wilcox et al., 2001Definitive
DFNB30MYO3AWalsh et al., 2002Walsh et al., 2002Strong
DFNB31WHRNMustapha et al., 2002Mburu et al., 2003Moderate
DFNB32/105CDC14A (see note 4)Masmoudi et al., 2003Delmaghani et al., 2016; Imtiaz et al., 2018Limited
DFNB33unknownMedlej-Hashim et al., 2002n/an/a
DFNB35ESRRBAnsar et al., 2003; Collin et al., 2008Collin et al., 2008Definitive
DFNB36ESPNNaz et al., 2004Naz et al., 2004Definitive
DFNB37MYO6 (see note 5)Ahmed et al., 2003Ahmed et al., 2003not reviewed
DFNB38unknownAnsar et al., 2003n/an/a
DFNB39HGFSchultz et al., 2009Schultz et al., 2009Moderate
DFNB40unknownDelmaghani et al., 2003n/an/a
DFNB42ILDR1Aslam et al., 2005Borck et al., 2011Definitive
DFNB44ADCY1Ansar et al., 2004Santos-Cortez et al., 2014Limited
DFNB45unknownBhatti et al., 2008n/an/a
DFNB46unknownMir et al., 2005n/an/a
DFNB47unknownHassan et al., 2006n/an/a
DFNB48CIB2Ahmad et al., 2005Riazuddin et al., 2012Definitive
DFNB49MARVELD2Ramzan et al., 2005Riazuddin et al., 2006Definitive
DFNB49/112BDP1Girotto et al., 2013Girotto et al., 2013Limited
DFNB51unknownShaikh et al., 2005n/an/a
DFNB53COL11A2Chen et al., 2005Chen et al., 2005Moderate
DFNB55unknownIrshad et al., 2005n/an/a
DFNB57PDZD7Booth et al., 2015Booth et al., 2015Definitive
DFNB59PJVKDelmaghani et al., 2006Delmaghani et al., 2006Definitive
DFNB60SLC22A4Ben Said et al., 2016Ben Said et al., 2016not reviewed
DFNB61SLC26A5Liu et al., 2003Liu et al., 2003Limited
DFNB62unknownAli et al., 2006n/an/a
DFNB63LRTOMT/COMT2Khan et al., 2007; Tlili et al., 2007Du et al., 2008Definitive
DFNB65unknownTariq et al., 2006n/an/a
DFNB66DCDC2Tlili et al., 2005Grati et al., 2015Limited
DFNB67LHFPL5Shabbir et al., 2006Shabbir et al., 2006; Kalay et al., 2006Definitive
DFNB68S1PR2Santos et al., 2006; Santos-Cortez et al., 2016Santos-Cortez et al., 2016Strong
DFNB70PNPT1von Ameln et al., 2012von Ameln et al., 2012not reviewed
DFNB71unknownChishti et al., 2009n/an/a
DFNB73BSNDRiazuddin et al., 2009Riazuddin et al., 2009Definitive
DFNB74MSRB3Waryah et al., 2009Ahmed et al., 2011Definitive
DFNB76SYNE4Horn et al., 2013Horn et al., 2013Moderate
DFNB77LOXHD1Grillet et al., 2009Grillet et al., 2009Definitive
DFNB79TPRNKhan et al., 2010Rehman et al., 2010Li et al., 2010Definitive
DFNB80unknownMosrati et al., 2013n/an/a
DFNB81unknownRehman et al., 2011n/an/a
DFNB82GPSM2 (see note 6)Shahin et al., 2010Walsh et al., 2010not reviewed
DFNB83unknownShahin et al., 2010n/an/a
DFNB84APTPRQShahin et al., 2010Schraders et al., 2010Definitive
DFNB84BOTOGLShahin et al., 2010Yariz et al., 2012Definitive
DFNB85unknownShahin et al., 2010n/an/a
DFNB86TBC1D24 (see note 7)Ali et al., 2012Rehman et al., 2014Definitive
DFNB88ELMOD3Jaworek et al., 2013Jaworek et al., 2013Limited
DFNB89KARS1Basit et al., 2011Santos-Cortez et al., 2013Limited
DFNB90unknownAli et al., 2011n/an/a
DFNB91SERPINB6Sirmaci et al., 2010Sirmaci et al., 2010Moderate
DFNB93CABP2Tabatabaiefar et al., 2011Schrauwen et al., 2012Definitive
DFNB94NARS2Simon et al., 2015Simon et al., 2015Limited
DFNB96unknownAnsar et al., 2011n/an/a
DFNB97METMujtaba et al., 2015Mujtaba et al., 2015Limited
DFNB98TSPEAR (see note 8)Delmaghani et al., 2012; Bowles et al., 2021Delmaghani et al., 2012; Bowles et al., 2021Disputed
DFNB99TMEM132ECheng et al., 2003Li et al., 2015Limited
DFNB100PPIP5K2Yousaf et al., 2018Yousaf et al., 2018not reviewed
DFNB101GRXCR2Imtiaz et al., 2014Imtiaz et al., 2014Moderate
DFNB102EPS8Behlouli et al., 2014Behlouli et al., 2014Moderate
DFNB103CLIC5Seco et al., 2015Seco et al., 2015not reviewed
DFNB104RIPOR2/FAM65BDiaz-Horta et al., 2014Diaz-Horta et al., 2014Moderate
DFNB106EPS8L2Dahmani et al., 2015Dahmani et al., 2015Moderate
DFNB107WBP2Buniello et al., 2016Buniello et al., 2016Limited
DFNB108ROR1 (see note 9)Diaz-Horta et al., 2016Diaz-Horta et al., 2016Limited
DFNB109ESRP1Rohacek et al., 2017Rohacek et al., 2017not reviewed
DFNB110COCHJanssensdeVarebeke et al., 2018JanssensdeVarebeke et al., 2018not reviewed
DFNB111MPZL2Wesdorp et al., 2018; Bademci et al., 2018Wesdorp et al., 2018Strong
DFNB113CEACAM16Booth et al., 2018Booth et al., 2018Strong
DFNB114GRAPLi et al., 2019Li et al., 2019not reviewed
DFNB115SPNS2Ingham et al., 2019Ingham et al., 2019not reviewed
DFNB116CLDN9Sineni et al., 2019Sineni et al., 2019not reviewed
DFNB117CLRN2Vona et al., 2021Vona et al., 2021not reviewed
DFNB118GDF6Bademci et al., 2020Bademci et al., 2020not reviewed
DFNB119AFG2BRichard et al., 2021Richard et al., 2021not reviewed
DFNB120MINAR2Bademci et al., 2022Bademci et al., 2022not reviewed
DFNB121GPR156Greene et al., 2023Greene et al., 2023not reviewed
DFNB122TMTC4Li et al., 2023Li et al., 2023not reviewed
DFNB123STX4Schrauwen et al., 2023Schrauwen et al., 2023not reviewed
unassignedCEMIPAbe et al., 2003Abe et al., 2003Disputed
unassignedUSH1GShearer et al., 2013Shearer et al., 2013Disputed
unassignedLRP5Xia et al., 2017Xia et al., 2017not reviewed
unassignedGAS2Chen et al., 2021Chen et al., 2021not reviewed
unassignedGOSR2Aburayyan et al., 2023Aburayyan et al., 2023not reviewed
unassignedCEP250Kang et al., 2023Kang et al., 2023not reviewed
unassignedPKHD1L1Redfield et al., 2024Redfield et al., 2024not reviewed

n/a = not applicable

Note 1: GIPC3 is responsible for progressive sensorineural hearing loss that can be associated with audiogenic seizures.

Note 2: STRC causes deafness-infertility syndrome in males when deleted in conjunction with CATSPER2 (Zhang et al., 2007).

Note 3: DFNB26 is suppressed by dominant modifier DFNM1.

Note 4: Some variants in CDC14A cause hearing impairment infertile male syndrome (HIIMS).

Note 5: MYO6-related hearing loss is likely semidominant.

Note 6: GPSM2 was initially reported as a nonsyndromic hearing loss gene but later determined to cause Chudley-McCullough syndrome, see Diaz-Horta et al., 2012 and Doherty et al., 2012.

Note 7: Autosomal recessive phenotypes of TBC1D24 are a spectrum of DOORS syndrome.

Note 8: TSPEAR has been called into question as a hearing loss gene.  Bowles et al., 2021 reports that the primary phenotypes associated with biallelic TSPEAR variants are tooth agenesis and ectodermal dysplasia, not hearing loss.  It also notes that the TSPEAR variants initially reported by Delmaghani et al., 2012 to segregate with hearing loss have since been observed in normal-hearing individuals, and suggests the true hearing loss variants may not have been recognized due to test limitations.

Note 9: ROR1 is responsible for autosomal recessive hearing loss associated with common cavity inner ear malformations and auditory neuropathy.