M1AP

protein-coding

meiosis 1 associated protein

Gene summary

This gene encodes a protein that is likely to function in progression of meiosis. A similar protein in mouse plays a role in gametogenesis in both sexes. Alternate splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

Previous symbols:

C2orf65

MANE transcript

NM_001321739.2

Inheritance

ClinVar variants

P:6U:84B:10

Top phenotype

Spermatogenic failure 48

gnomAD constraint

pLI —, LoF o/e 1.02

Max pathogenic AF

—

Genomic locus

chr2:74,557,883-74,648,338

External References & Databases

Ensembl (ENSG00000159374)

Transcript & Mutation Effects

hg38 • Region Span ~90.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spermatogenic failure 48LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0030846

Submitter: Labcorp Genetics (formerly Invitae)

spermatogenic failure 48STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030846

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Spermatogenic failure 48AR

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: 32017041; 32673564

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to M1AP variants in ClinVar

9 Conditions Cataloged

not specifiedTotal: 80

Spermatogenic failure 48Total: 10

not providedTotal: 8

Non-obstructive azoospermiaTotal: 6

M1AP-related conditionTotal: 2

CryptozoospermiaTotal: 1

Male infertility with azoospermia or oligozoospermia due to single gene mutationTotal: 1

Male infertilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001321739.2. 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			1 clinvar	3 clinvar		4
missense		1 clinvar	81 clinvar	7 clinvar		89
nonsense		1 clinvar	1 clinvar			2
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)	2 clinvar	1 clinvar	1 clinvar			4
Total	3	3	84	10	0	100

Highest pathogenic variant AF is 0.003327088

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001321739.2	RefSeq	NP_001308668.1	10	MANE Select
ENST00000421985.2	Ensembl	ENSP00000414882.2	10	MANE Select
NM_001281295.2	RefSeq	NP_001268224.1	6	Standard
NM_001281296.2	RefSeq	NP_001268225.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

RNA processing
meiosis I
spermatogenesis
female gamete generation
cell differentiation

Molecular Function

molecular_function
protein binding
identical protein binding

Cellular Component

cytoplasm
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000290536
Coding exons: 10
Length: 90456
Individuals with no LoFs: 125621
Homozygous LoFs: 0
Heterozygous LoFs: 127
Defined: 125748
p: 0.000505

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.613	265	295	0.900	0.0000151	3461
Missense (PolyPhen)		93	103.35	0.89988		1220
Synonymous	-0.284	123	119	1.03	0.00000650	1067
Loss of Function	-0.119	28	27.3	1.02	0.00000153	286

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0015	0.0015	notable
Latino/Admixed American	0.00029	0.00029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00034	0.00034	rare
South Asian	0.0016	0.0016	notable
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for meiosis I progression during spermatogenesis. {ECO:0000250}.;

Recessive Scores

pRec: 0.0901

Intolerance Scores

RVIS EVS: -0.42
RVIS percentile EVS: 25.64

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N

Gene Damage Prediction

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