SHOC1

protein-coding

shortage in chiasmata 1

Gene summary

Enables ATP hydrolysis activity and single-stranded DNA binding activity. Predicted to be involved in resolution of meiotic recombination intermediates and synaptonemal complex assembly. Predicted to be located in chromosome. Predicted to be active in condensed nuclear chromosome. Implicated in spermatogenic failure 75. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

C9orf84

MANE transcript

NM_001378211.1

Inheritance

ClinVar variants

P:12U:18B:6

Top phenotype

Spermatogenic failure 75

gnomAD constraint

pLI —, LoF o/e 0.66

Max pathogenic AF

—

Genomic locus

chr9:111,686,171-111,795,008

External References & Databases

Ensembl (ENSG00000165181)

Transcript & Mutation Effects

hg38 • Region Span ~108.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spermatogenic failureLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0004983

Submitter: Franklin by Genoox

Two Chinese families with infertility underwent DNA examination which revealed compound heterozygous loss of function variants of SHOC1 (c.C1582T:p.R528X and c.231_232del:p.L78Sfs*9, respectively) in family 1. In family 2, homozygous LoF variant in SHOC1 (c.1194delA:p.L400Cfs*7) was identified in the siblings with infertility.

Clinical Genomic Database (CGD)

Spermatogenic failure 75AR

Manifestation: Genitourinary

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 32741963; 32900840; 35485979

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SHOC1 variants in ClinVar

6 Conditions Cataloged

Inborn genetic diseasesTotal: 11

not providedTotal: 8

Spermatogenic failure 75Total: 8

Male infertilityTotal: 4

SHOC1-related conditionTotal: 1

Non-obstructive azoospermiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001378211.1. 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			1 clinvar	4 clinvar		5
missense	1 clinvar		16 clinvar	2 clinvar		19
nonsense	1 clinvar	2 clinvar				3
start loss						0
frameshift	7 clinvar					7
splice donor/acceptor (+/-2bp)	1 clinvar		1 clinvar			2
Total	10	2	18	6	0	36

Highest pathogenic variant AF is 0.000029278492

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001378211.1	RefSeq	NP_001365140.1	27	MANE Select
ENST00000682961.1	Ensembl	ENSP00000508388.1	27	MANE Select
NM_001080551.3	RefSeq	NP_001074020.3	24	Standard
NM_001378212.1	RefSeq	NP_001365141.1	23	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

resolution of meiotic recombination intermediates

Molecular Function

single-stranded DNA binding
ATPase activity

Cellular Component

condensed nuclear chromosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000374287
Coding exons: 25
Length: 108836
Individuals with no LoFs: 125650
Homozygous LoFs: 0
Heterozygous LoFs: 94
Defined: 125744
p: 0.000374

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.32	582	679	0.857	0.0000312	9488
Missense (PolyPhen)		134	161.34	0.83056		2339
Synonymous	2.35	197	244	0.809	0.0000115	2588
Loss of Function	2.60	45	68.2	0.660	0.00000304	989

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.0016	0.0016	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00023	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00021	0.00020	rare
South Asian	0.00028	0.00026	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: ATPase required during meiosis for the formation of crossover recombination intermediates (By similarity). Binds DNA: preferentially binds to single-stranded DNA and DNA branched structures (PubMed:29742103). Does not show nuclease activity in vitro, but shows ATPase activity, which is stimulated by the presence of single-stranded DNA (PubMed:29742103). {ECO:0000250|UniProtKB:A2ALV5, ECO:0000269|PubMed:29742103}.;

Intolerance Scores

RVIS EVS: 2.5
RVIS percentile EVS: 98.65

Essentials

Essential (gene trap): N