SPATA2

protein-coding

spermatogenesis associated 2, the group of Protein phosphatase 1 regulatory subunits

Gene summary

Enables signaling receptor complex adaptor activity and ubiquitin-specific protease binding activity. Involved in several processes, including protein deubiquitination; regulation of necroptotic process; and regulation of tumor necrosis factor-mediated signaling pathway. Located in cytoplasm. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_006038.4

Inheritance

—

ClinVar variants

U:87B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.06

Max pathogenic AF

—

Genomic locus

chr20:49,903,391-49,915,529

External References & Databases

Ensembl (ENSG00000158480)

Transcript & Mutation Effects

hg38 • Region Span ~12.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SPATA2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 89

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006038.4. 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		1
missense			86 clinvar	3 clinvar		89
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	87	4	0	91

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006038.4	RefSeq	NP_006029.1	2	MANE Select
ENST00000289431.10	Ensembl	ENSP00000289431.5	2	MANE Select
NM_001135773.2	RefSeq	NP_001129245.1	2	Standard
ENST00000422556.1	Ensembl	ENSP00000416799.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Necroptosis - Homo sapiens (human)

Biological Process

multicellular organism development
spermatogenesis
regulation of tumor necrosis factor-mediated signaling pathway
programmed cell death
regulation of inflammatory response

Molecular Function

molecular_function
protein binding

Cellular Component

fibrillar center
nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000422556
Coding exons: 2
Length: 12153
Individuals with no LoFs: 125593
Homozygous LoFs: 1
Heterozygous LoFs: 3
Defined: 125597
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.677	305	340	0.897	0.0000230	3349
Missense (PolyPhen)		105	139.41	0.75315		1265
Synonymous	1.16	134	152	0.880	0.0000105	1091
Loss of Function	3.50	1	16.2	0.0617	9.35e-7	193

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000091	0.0000088	rare
South Asian	0	0.0	absent
Other	0.00033	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Bridging factor that mediates the recruitment of CYLD to the LUBAC complex, thereby regulating TNF-alpha-induced necroptosis (PubMed:27307491, PubMed:27458237, PubMed:27545878, PubMed:27591049). Acts as a direct binding intermediate that bridges RNF31/HOIP, the catalytic subunit of the LUBAC complex, and the deubiquitinase (CYLD), thereby recruiting CYLD to the TNF- R1 signaling complex (TNF-RSC) (PubMed:27458237, PubMed:27545878, PubMed:27591049). Required to activate the 'Met-1'- (linear) and 'Lys-63'-linked deubiquitinase activities of CYLD (PubMed:27458237, PubMed:27591049). Controls the kinase activity of RIPK1 and TNF-alpha-induced necroptosis by promoting 'Met-1'- linked deubiquitination of RIPK1 by CYLD (By similarity). {ECO:0000250|UniProtKB:Q8K004, ECO:0000269|PubMed:27307491, ECO:0000269|PubMed:27458237, ECO:0000269|PubMed:27545878, ECO:0000269|PubMed:27591049}.;

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.263
RVIS EVS: -0.86
RVIS percentile EVS: 10.85

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.917

Gene Damage Prediction

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