SOHLH1

protein-coding

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

Gene summary

This gene encodes one of testis-specific transcription factors which are essential for spermatogenesis, oogenesis and folliculogenesis. This gene is located on chromosome 9. Mutations in this gene are associated with nonobstructive azoospermia. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2013]

Previous symbols:

C9orf157

MANE transcript

NM_001101677.2

Inheritance

AR, AD

ClinVar variants

P:6U:68B:26

Top phenotype

Ovarian dysgenesis 5

gnomAD constraint

pLI —, LoF o/e 0.43

Max pathogenic AF

—

Genomic locus

chr9:135,693,407-135,704,498

External References & Databases

Ensembl (ENSG00000165643)

Transcript & Mutation Effects

hg38 • Region Span ~11.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

ovarian dysgenesis 5STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0054666

Submitter: Labcorp Genetics (formerly Invitae)

ovarian dysgenesis 5LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0054666

Submitter: Ambry Genetics

spermatogenic failure 32STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0020855

Submitter: PanelApp Australia

hypogonadismLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0002146

Submitter: Ambry Genetics

ovarian dysgenesis 5STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0054666

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Ovarian dysgenesis 5AR

Manifestation: Endocrine; Genitourinary

Intervention: Endocrine

Rationale: Awareness may allow medical management (eg, with combined estrogen-progestin therapy) in order to benefit pubertal development and growth

Refs: 20506135; 25774885; 28718531

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SOHLH1 variants in ClinVar

8 Conditions Cataloged

not specifiedTotal: 72

not providedTotal: 20

Ovarian dysgenesis 5Total: 8

SOHLH1-related disorderTotal: 7

Spermatogenic failure 32Total: 5

Nonsyndromic hypergonadotropic hypogonadismTotal: 2

Spermatogenic FailureTotal: 1

Genetic non-acquired premature ovarian failureTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001101677.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				8 clinvar	1 clinvar	9
missense		1 clinvar	67 clinvar	12 clinvar	5 clinvar	85
nonsense	1 clinvar	3 clinvar				4
start loss						0
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	1	5	68	20	6	100

Highest pathogenic variant AF is 0.000015891419

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001101677.2	RefSeq	NP_001095147.2	8	MANE Select
ENST00000425225.2	Ensembl	ENSP00000404438.1	8	MANE Select
NM_001012415.3	RefSeq	NP_001012415.3	7	Standard
ENST00000298466.9	Ensembl	ENSP00000298466.5	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

multicellular organism development
spermatogenesis
oocyte differentiation
cell differentiation
positive regulation of transcription by RNA polymerase II

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

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000425225
Coding exons: 8
Length: 6122
Individuals with no LoFs: 124763
Homozygous LoFs: 5
Heterozygous LoFs: 720
Defined: 125488
p: 0.00289

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.724	276	244	1.13	0.0000164	2405
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.0098	0.0098	notable
Finnish	0.015	0.015	notable
European (Non-Finnish)	0.0016	0.0015	notable
South Asian	0.00095	0.00095	rare
Other	0.0036	0.0034	notable

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.108

Gene Damage Prediction

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