REC8

protein-coding

REC8 meiotic recombination protein, the group of Kleisins|Cohesin complex

Gene summary

This gene encodes a member of the kleisin family of SMC (structural maintenance of chromosome) protein partners. The protein localizes to the axial elements of chromosomes during meiosis in both oocytes and spermatocytes. In the mouse, the homologous protein is a key component of the meiotic cohesion complex, which regulates sister chromatid cohesion and recombination between homologous chromosomes. Multiple alternatively spliced variants, encoding the same protein, have been found for this gene. [provided by RefSeq, Jul 2008]

Previous symbols:

REC8L1

MANE transcript

NM_001048205.2

Inheritance

ClinVar variants

P:3U:29B:4

Top phenotype

Premature ovarian insufficiency

gnomAD constraint

pLI —, LoF o/e 0.42

Max pathogenic AF

—

Genomic locus

chr14:24,171,853-24,180,257

External References & Databases

Ensembl (ENSG00000100918)

Transcript & Mutation Effects

hg38 • Region Span ~8.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

primary ovarian failureMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0005387

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to REC8 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 19

not providedTotal: 7

Premature ovarian insufficiencyTotal: 3

Premature ovarian failureTotal: 1

AzoospermiaTotal: 1

Non-obstructive azoospermiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001048205.2. 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					2 clinvar	2
missense			23 clinvar	2 clinvar		25
nonsense						0
start loss						0
frameshift	1 clinvar	1 clinvar				2
splice donor/acceptor (+/-2bp)		1 clinvar	6 clinvar			7
Total	1	2	29	2	2	36

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001048205.2	RefSeq	NP_001041670.1	19	MANE Select
ENST00000611366.5	Ensembl	ENSP00000482439.1	19	MANE Select
NM_005132.3	RefSeq	NP_005123.2	19	Standard
ENST00000557806.5	Ensembl	ENSP00000453763.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Oocyte meiosis - Homo sapiens (human)
Reproduction
Meiotic synapsis
Meiosis
Cell Cycle

Biological Process

double-strand break repair via homologous recombination
oocyte maturation
double-strand break repair
sister chromatid cohesion
synaptonemal complex assembly

Molecular Function

chromatin binding

Cellular Component

condensed nuclear chromosome kinetochore
lateral element
male germ cell nucleus
nucleus
meiotic cohesin complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000311457
Coding exons: 19
Length: 8402
Individuals with no LoFs: 124755
Homozygous LoFs: 0
Heterozygous LoFs: 46
Defined: 124801
p: 0.000184

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.47	265	342	0.776	0.0000215	3474
Missense (PolyPhen)		76	115.24	0.65952		1158
Synonymous	0.127	131	133	0.986	0.00000816	1146
Loss of Function	3.17	15	35.3	0.425	0.00000183	385

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00017	0.00011	rare
Finnish	0.000093	0.000093	rare
European (Non-Finnish)	0.00027	0.00027	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required during meiosis for separation of sister chromatids and homologous chromosomes. Proteolytic cleavage of REC8 on chromosome arms by separin during anaphase I allows for homologous chromosome separation in meiosis I and cleavage of REC8 on centromeres during anaphase II allows for sister chromatid separation in meiosis II (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.0921

Intolerance Scores

RVIS EVS: -0.31
RVIS percentile EVS: 32.06

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.540

Gene Damage Prediction

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