SMC1B

protein-coding

structural maintenance of chromosomes 1B, the group of Structural maintenance of chromosomes proteins|Cohesin complex

Gene summary

SMC1L2 belongs to a family of proteins required for chromatid cohesion and DNA recombination during meiosis and mitosis (3:Revenkova et al., 2001 [PubMed 11564881]).[supplied by OMIM, Mar 2008]

Previous symbols:

SMC1L2

MANE transcript

NM_148674.5

Inheritance

ClinVar variants

P:1U:140B:13

Top phenotype

Myoepithelial tumor

gnomAD constraint

pLI —, LoF o/e 0.24

Max pathogenic AF

—

Genomic locus

chr22:45,344,063-45,413,619

External References & Databases

Ensembl (ENSG00000077935)

Transcript & Mutation Effects

hg38 • Region Span ~69.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

gonadal dysgenesisLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0001967

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SMC1B variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 139

not providedTotal: 8

Myoepithelial tumorTotal: 1

Genetic non-acquired premature ovarian failureTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_148674.5. 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			2 clinvar	4 clinvar	3 clinvar	9
missense		1 clinvar	136 clinvar	5 clinvar	1 clinvar	143
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	1	140	9	4	154

Highest pathogenic variant AF is 0.000013156263

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_148674.5	RefSeq	NP_683515.4	25	MANE Select
ENST00000357450.9	Ensembl	ENSP00000350036.4	25	MANE Select
NM_001291501.2	RefSeq	NP_001278430.1	23	Standard
ENST00000404354.3	Ensembl	ENSP00000385902.3	23	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

sister chromatid cohesion
meiotic cell cycle

Molecular Function

DNA binding
ATP binding

Cellular Component

chromosome, centromeric region
lateral element
nucleoplasm
cytosol
meiotic cohesin complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000357450
Coding exons: 25
Length: 69557
Individuals with no LoFs: 124760
Homozygous LoFs: 0
Heterozygous LoFs: 34
Defined: 124794
p: 0.000136

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.95	486	623	0.781	0.0000316	8194
Missense (PolyPhen)		132	208.99	0.63161		2798
Synonymous	0.970	198	216	0.916	0.0000109	2143
Loss of Function	5.92	17	70.8	0.240	0.00000389	884

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0.000066	0.000058	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.000058	0.000056	rare
Finnish	0.000093	0.000093	rare
European (Non-Finnish)	0.00021	0.00020	rare
South Asian	0.000068	0.000065	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Meiosis-specific component of cohesin complex. Required for the maintenance of meiotic cohesion, but not, or only to a minor extent, for its establishment. Contributes to axial element (AE) formation and the organization of chromatin loops along the AE. Plays a key role in synapsis, recombination and chromosome movements. The cohesin complex is required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The meiosis-specific cohesin complex probably replaces mitosis specific cohesin complex when it dissociates from chromatin during prophase I (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.0847

Intolerance Scores

LoFtool: 0.366
RVIS EVS: 0.27
RVIS percentile EVS: 70.73

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.159

Gene Damage Prediction

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