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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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SOHLH1
spermatogenesis and oogenesis specific basic helix-loop-helix 1
Chromosome 9 Β· 9q34.3
NCBI Gene: 402381Ensembl: ENSG00000165643.12HGNC: HGNC:27845UniProt: Q5JUK2
21PubMed Papers
22Diseases
0Drugs
5Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingcell differentiationnucleuschromatinazoospermia46,XX gonadal dysgenesisprimary ovarian insufficiencyneurodegenerative disease
✦AI Summary

SOHLH1 is a germ cell-specific basic helix-loop-helix (bHLH) transcription factor that plays a critical role in both male and female reproductive development 1. In males, SOHLH1 suppresses spermatogonial stem cell maintenance genes while inducing spermatogonial differentiation 2. In females, it coordinates oocyte growth and differentiation during early folliculogenesis 3. SOHLH1 functions through complex regulatory networks, forming heterodimers with SOHLH2 and interacting with SP1 to auto-regulate its own expression through E-boxes and GC-boxes in its promoter 1. The protein also directly represses STRA8 expression, helping coordinate the timing of meiotic entry 4. SOHLH1 cooperates with other transcription factors including FIGLA and LHX8 in regulating oocyte development networks 3. Loss-of-function mutations in SOHLH1 cause hypergonadotropic hypogonadism, resulting in ovarian dysgenesis and spermatogenic failure in humans 5. Beyond reproductive dysfunction, SOHLH1 deficiency affects immune profiles, metabolism, and behavior in mice, suggesting broader physiological roles 6. This transcription factor represents a key regulator of germline differentiation with potential therapeutic implications for infertility disorders.

Sources cited
1
SOHLH1 is a germ cell-specific bHLH transcription factor that forms heterodimers with SOHLH2 and auto-regulates through E-boxes and GC-boxes
PMID: 25003626
2
SOHLH1 suppresses spermatogonial stem cell maintenance genes while promoting spermatogonial differentiation
PMID: 39295530
3
SOHLH1 coordinates oocyte growth and differentiation, cooperating with FIGLA and LHX8 in regulatory networks
PMID: 32086523
4
SOHLH1 directly represses STRA8 expression through E-box motifs, coordinating meiotic timing
PMID: 25603532
5
SOHLH1 mutations are associated with ovarian dysgenesis and primary ovarian insufficiency
PMID: 34794894
6
SOHLH1 deficiency causes hypergonadotropic hypogonadism and affects immune profiles, metabolism, and behavior beyond reproductive dysfunction
PMID: 36723967
Disease Associationsβ“˜22
azoospermiaOpen Targets
0.62Moderate
46,XX gonadal dysgenesisOpen Targets
0.61Moderate
primary ovarian insufficiencyOpen Targets
0.39Weak
neurodegenerative diseaseOpen Targets
0.32Weak
genetic non-acquired premature ovarian failureOpen Targets
0.26Weak
breast ductal adenocarcinomaOpen Targets
0.11Weak
adolescent idiopathic scoliosisOpen Targets
0.07Suggestive
partial chromosome Y deletionOpen Targets
0.07Suggestive
gliomaOpen Targets
0.07Suggestive
spermatogenic failure, X-linked, 2Open Targets
0.07Suggestive
46,XX testicular disorder of sex developmentOpen Targets
0.07Suggestive
spermatogenic failure 57Open Targets
0.06Suggestive
spermatogenic failure 50Open Targets
0.06Suggestive
spermatogenic failure 25Open Targets
0.06Suggestive
spermatogenic failure 71Open Targets
0.06Suggestive
46,XY complete gonadal dysgenesisOpen Targets
0.06Suggestive
male infertility with azoospermia or oligozoospermia due to single gene mutationOpen Targets
0.06Suggestive
spermatogenic failure 12Open Targets
0.06Suggestive
spermatogenic failure 63Open Targets
0.06Suggestive
ring chromosome YOpen Targets
0.06Suggestive
Ovarian dysgenesis 5UniProt
Spermatogenic failure 32UniProt
Pathogenic Variants5
NM_001101677.2(SOHLH1):c.27C>G (p.Tyr9Ter)Pathogenic
Nonsyndromic hypergonadotropic hypogonadism|Ovarian dysgenesis 5
β˜…β˜…β˜†β˜†2018β†’ Residue 9
NM_001101677.2(SOHLH1):c.745C>T (p.Gln249Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2017β†’ Residue 249
NM_001101677.2(SOHLH1):c.705del (p.Lys236fs)Likely pathogenic
Nonsyndromic hypergonadotropic hypogonadism|Ovarian dysgenesis 5
β˜…β˜†β˜†β˜†2015β†’ Residue 236
NM_001101677.2(SOHLH1):c.397C>T (p.Gln133Ter)Likely pathogenic
Ovarian dysgenesis 5
β˜†β˜†β˜†β˜†2023β†’ Residue 133
NM_001101677.2(SOHLH1):c.244C>G (p.Gln82Glu)Likely pathogenic
Genetic non-acquired premature ovarian failure
β˜†β˜†β˜†β˜†2019β†’ Residue 82
View on ClinVar β†—
Related Genes
GBX1Protein interaction96%YBX2Protein interaction90%NOBOXProtein interaction90%SOHLH2Protein interaction83%STRA8Protein interaction74%CCDC169-SOHLH2Protein interaction73%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
7%
Ovary
4%
Liver
1%
Heart
0%
Lung
0%
Gene Interaction Network
Click a node to explore
SOHLH1GBX1YBX2NOBOXSOHLH2STRA8CCDC169-SOHLH2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q5JUK2
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.98LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.69 [0.49–0.98]
RankingsWhere SOHLH1 stands among ~20K protein-coding genes
  • #14,023of 20,598
    Most Researched21
  • #3,636of 5,498
    Most Pathogenic Variants5
  • #9,367of 17,882
    Most Constrained (LOEUF)0.98
Genes detectedSOHLH1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Genetics of ovarian insufficiency and defects of folliculogenesis.
PMID: 34794894
Best Pract Res Clin Endocrinol Metab Β· 2022
1.00
2
Short Chain Chlorinated Paraffins Impaired Spermatogenesis Process in Mice via Inhibiting Ξ±-KG/TET Enzyme Activity.
PMID: 39295530
Environ Sci Technol Β· 2024
0.90
3
Auto-regulation of the Sohlh1 gene by the SOHLH2/SOHLH1/SP1 complex: implications for early spermatogenesis and oogenesis.
PMID: 25003626
PLoS One Β· 2014
0.80
4
Immunohistochemical Study of Expression of Sohlh1 and Sohlh2 in Normal Adult Human Tissues.
PMID: 26375665
PLoS One Β· 2015
0.70
5
FIGLA, LHX8 and SOHLH1 transcription factor networks regulate mouse oocyte growth and differentiation.
PMID: 32086523
Nucleic Acids Res Β· 2020
0.60