SMC1B

Chr 22

structural maintenance of chromosomes 1B

Also known as: SMC1BETA, SMC1L2

NCBI Gene: 27127 ENSG00000077935 UniProt: Q8NDV3 OMIM: 608685

SMC1B encodes a meiosis-specific component of the cohesin complex that maintains sister chromatid cohesion during meiosis and contributes to chromosome synapsis and recombination. Mutations cause male infertility due to meiotic arrest and azoospermia, following an X-linked recessive inheritance pattern. The gene shows significant constraint against loss-of-function variants (LOEUF 0.36), reflecting its essential role in male reproductive development.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.36

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.36LOEUF

pLI 0.104

Z-score 5.92

OE 0.24 (0.16–0.36)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.95Z-score

OE missense 0.78 (0.72–0.84)

486 obs / 622.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.24 (0.16–0.36)

0≤0.351.4

Missense OE?0.78 (0.72–0.84)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 17 / 70.8Missense obs/exp: 486 / 622.6Syn Z: 0.97

Background carrier burden — how many people carry a rare variant somewhere in SMC1B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 60

1,248 rare PASS variants

Rare truncating (LoF)

1 in 1,600

144 rare PASS variants

Rare synonymous (reference)

1 in 80

479 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SMC1B. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 85	1 in 1,600
South Asian	~43k	1 in 44	1 in 2,200
Remaining (unassigned)	~30k	1 in 48	1 in 1,100
European (Finnish)	~27k	1 in 130	1 in 2,000
Admixed American	~22k	1 in 61	1 in 2,300
African / African American	~21k	1 in 52	1 in 1,700
East Asian	~20k	1 in 54	1 in 2,200
Ashkenazi Jewish	~13k	1 in 160	1 in 1,600
Middle Eastern	~2,884	1 in 40	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 21 of 25 coding exons well covered in gnomAD exomes; exons 2, 8, 15, 16 marginal. Genomes: all 25.? see exons ↓