GCNA

protein-coding

germ cell nuclear acidic peptidase

Gene summary

Enables SUMO polymer binding activity. Involved in protein-DNA covalent cross-linking repair. Located in PML body. Implicated in X-linked spermatogenic failure 4. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

ACRC

MANE transcript

NM_052957.5

Inheritance

ClinVar variants

P:4U:154B:21

Top phenotype

Spermatogenic failure, X-linked, 4

gnomAD constraint

pLI —, LoF o/e 0.06

Max pathogenic AF

—

Genomic locus

chrX:71,578,437-71,613,583

External References & Databases

Ensembl (ENSG00000147174)

Transcript & Mutation Effects

hg38 • Region Span ~35.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spermatogenic failure, X-linked, 4STRONG

Inheritance Pattern: XL

Disease ID:MONDO:0024773

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Spermatogenic failure, X-linked, 4XL

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: 33963445; 34413498; 35172124

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GCNA variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 103

not providedTotal: 14

Spermatogenic failure, X-linked, 4Total: 4

Non-obstructive azoospermiaTotal: 2

AzoospermiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_052957.5. 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			5 clinvar	7 clinvar		12
missense	1 clinvar		131 clinvar	14 clinvar		146
nonsense	1 clinvar		3 clinvar			4
start loss						0
frameshift	1 clinvar	1 clinvar				2
splice donor/acceptor (+/-2bp)			15 clinvar			15
Total	3	1	154	21	0	179

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_052957.5	RefSeq	NP_443189.1	12	MANE Select
ENST00000373696.8	Ensembl	ENSP00000362800.3	12	MANE Select
ENST00000373695.1	Ensembl	ENSP00000362799.1	12	Standard
ENST00000373695.2	Ensembl	ENSP00000362799.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373695
Coding exons: 12
Length: 35173
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.745	247	282	0.875	0.0000245	4661
Missense (PolyPhen)		2	3.97	0.50377		66
Synonymous	0.691	118	128	0.922	0.0000139	1205
Loss of Function	3.68	1	17.7	0.0564	0.00000125	353

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0604

Intolerance Scores

RVIS EVS: -0.35
RVIS percentile EVS: 29.43

Essentials

Essential (gene trap): N