SOHLH1

spermatogenesis and oogenesis specific basic helix-loop-helix 1, the group of Basic helix-loop-helix proteins

Basic information

Region (hg38): 9:135693407-135704498

Previous symbols: [ "C9orf157" ]

Links

ENSG00000165643

∙ NCBI:402381 ∙ OMIM:610224 ∙ HGNC:27845 ∙ Uniprot:Q5JUK2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

ovarian dysgenesis 5 (Limited), mode of inheritance: AD
hypogonadism (Limited), mode of inheritance: AR
ovarian dysgenesis 5 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ovarian dysgenesis 5	AR	Endocrine	Awareness may allow medical management (eg, with combined estrogen-progestin therapy) in order to benefit pubertal development and growth	Endocrine; Genitourinary	20506135; 25774885; 28718531

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SOHLH1 gene.

not_specified (66 variants)
not_provided (19 variants)
Ovarian_dysgenesis_5 (7 variants)
SOHLH1-related_disorder (6 variants)
Spermatogenic_failure_32 (5 variants)
Nonsyndromic_hypergonadotropic_hypogonadism (2 variants)
Spermatogenic_Failure (1 variants)
Genetic_non-acquired_premature_ovarian_failure (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SOHLH1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001101677.2. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				7 clinvar	1 clinvar	8
missense		1 clinvar	61 clinvar	12 clinvar	5 clinvar	79
nonsense	1 clinvar	2 clinvar				3
start loss						0
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)				1 clinvar		1
Total	1	4	61	20	6

Highest pathogenic variant AF is 0.000012465455

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SOHLH1	protein_coding	protein_coding	ENST00000425225	8	6122

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00226	0.982	124763	5	720	125488	0.00289

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.724	276	244	1.13	0.0000164	2405
Missense in Polyphen		66	63.948	1.0321		590
Synonymous	-1.78	138	114	1.21	0.00000871	820
Loss of Function	2.11	7	16.2	0.433	7.64e-7	169

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000182	0.000181
Ashkenazi Jewish	0.0000998	0.0000994
East Asian	0.00980	0.00984
Finnish	0.0150	0.0147
European (Non-Finnish)	0.00156	0.00154
Middle Eastern	0.00980	0.00984
South Asian	0.000948	0.000948
Other	0.00361	0.00343

dbNSFP

Source: dbNSFP

Function: FUNCTION: Transcription regulator of both male and female germline differentiation. Suppresses genes involved in spermatogonial stem cells maintenance, and induces genes important for spermatogonial differentiation. Coordinates oocyte differentiation without affecting meiosis I (By similarity). {ECO:0000250|UniProtKB:Q6IUP1, ECO:0000250|UniProtKB:Q9D489}.;
Disease: DISEASE: Note=Genetic variations in SOHLH1 may be associated with non-obstructive azoospermia. {ECO:0000269|PubMed:20506135}.; DISEASE: Ovarian dysgenesis 5 (ODG5) [MIM:617690]: A disorder characterized by lack of spontaneous pubertal development, primary amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism as a result of streak gonads. ODG5 is an autosomal recessive condition. {ECO:0000269|PubMed:25774885}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.0856

Intolerance Scores

loftool: 0.499
rvis_EVS: 0.07
rvis_percentile_EVS: 59.04

Haploinsufficiency Scores

pHI: 0.0811
hipred: N
hipred_score: 0.173
ghis: 0.487

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.108

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Sohlh1
Phenotype: reproductive system phenotype; endocrine/exocrine gland phenotype;

Gene ontology

Biological process: multicellular organism development;spermatogenesis;oocyte differentiation;cell differentiation;positive regulation of transcription by RNA polymerase II
Cellular component: nucleus;cytoplasm
Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;protein homodimerization activity;protein heterodimerization activity