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 provided (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				6	2	8
missense			34	6	5	45
nonsense	1	1				2
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)					1	1
splice region			1			1
non coding					2	2
Total	1	2	34	12	10

Highest pathogenic variant AF is 0.0000197

Variants in SOHLH1

This is a list of pathogenic ClinVar variants found in the SOHLH1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-135693638-C-T		not specified	Uncertain significance (Apr 07, 2022)
9-135693644-G-C		not specified	Uncertain significance (Dec 03, 2024)
9-135693655-G-T		not specified	Uncertain significance (Feb 23, 2023)
9-135693679-G-A			Benign (Jan 24, 2018)
9-135693682-T-G		not specified	Uncertain significance (Nov 22, 2024)
9-135693683-C-T		not specified	Uncertain significance (Mar 18, 2024)
9-135693688-G-C		not specified	Uncertain significance (Apr 06, 2024)
9-135693771-T-C			Likely benign (May 01, 2022)
9-135693776-C-T		not specified	Uncertain significance (Mar 29, 2024)
9-135693779-A-G		not specified	Likely benign (Oct 27, 2023)
9-135693781-G-A		not specified	Uncertain significance (Dec 12, 2023)
9-135693785-G-A		not specified	Uncertain significance (Apr 24, 2024)
9-135693796-C-T		not specified	Uncertain significance (Feb 21, 2024)
9-135693799-C-T		not specified	Uncertain significance (Sep 22, 2023)
9-135694389-G-A		not specified	Likely benign (Nov 08, 2024)
9-135694395-G-A		not specified	Uncertain significance (Jun 28, 2022)
9-135694417-G-T		not specified • SOHLH1-related disorder	Benign (Oct 01, 2024)
9-135694450-A-G		SOHLH1-related disorder	Likely benign (Nov 20, 2019)
9-135694452-G-A		not specified	Likely benign (Apr 07, 2023)
9-135695101-G-A		not specified	Likely benign (Jan 19, 2022)
9-135695135-G-C		not specified	Uncertain significance (Nov 14, 2023)
9-135695153-C-T		not specified	Uncertain significance (Oct 21, 2021)
9-135695154-G-A			Likely benign (Jun 15, 2018)
9-135695165-G-A		Ovarian dysgenesis 5;Spermatogenic failure 32	Uncertain significance (-)
9-135695180-G-A			Pathogenic (May 16, 2017)

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