GMCL1

protein-coding

germ cell-less 1, spermatogenesis associated, the group of BTB domain containing

Gene summary

This gene encodes a nuclear envelope protein that appears to be involved in spermatogenesis, either directly or by influencing genes that play a more direct role in the process. This multi-exon locus is the homolog of the mouse and drosophila germ cell-less gene but the human genome also contains a single-exon locus on chromosome 5 that contains an open reading frame capable of encoding a highly-related protein. [provided by RefSeq, Jul 2008]

MANE transcript

NM_178439.5

Inheritance

—

ClinVar variants

U:51B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.49

Max pathogenic AF

—

Genomic locus

chr2:69,829,660-69,881,384

External References & Databases

Ensembl (ENSG00000087338)

Transcript & Mutation Effects

hg38 • Region Span ~51.7 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 GMCL1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 48

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_178439.5. 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				1 clinvar		1
missense			47 clinvar		1 clinvar	48
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	51	1	1	53

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_178439.5	RefSeq	NP_848526.1	14	MANE Select
ENST00000282570.4	Ensembl	ENSP00000282570.3	14	MANE Select
ENST00000885038.1	Ensembl	ENSP00000555097.1	12	Standard
ENST00000885038.2	Ensembl	ENSP00000555097.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

multicellular organism development
spermatogenesis
cell differentiation

Molecular Function

protein binding
identical protein binding

Cellular Component

nuclear matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000282570
Coding exons: 14
Length: 51755
Individuals with no LoFs: 125702
Homozygous LoFs: 0
Heterozygous LoFs: 44
Defined: 125746
p: 0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.21	212	268	0.792	0.0000128	3366
Missense (PolyPhen)		31	53.742	0.57683		718
Synonymous	-0.678	100	91.7	1.09	0.00000424	914
Loss of Function	2.67	16	32.4	0.494	0.00000158	383

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000062	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0017	0.0010	notable
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00014	0.00013	rare
South Asian	0.00014	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Possible function in spermatogenesis. Enhances the degradation of MDM2 and increases the amount of p53 probably by modulating the nucleocytoplasmic transport (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.114

Intolerance Scores

LoFtool: 0.826
RVIS EVS: -0.45
RVIS percentile EVS: 24.19

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.699

Gene Damage Prediction

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