SMC4

Chr 3

structural maintenance of chromosomes 4

Also known as: CAP-C, CAPC, SMC-4, SMC4L1

NCBI Gene: 10051 ENSG00000113810 UniProt: Q9NTJ3 OMIM: 605575

This gene belongs to the 'structural maintenance of chromosomes' (SMC) gene family. Members of this gene family play a role in two changes in chromosome structure during mitotic segregation of chromosomes- chromosome condensation and sister chromatid cohesion. The protein encoded by this gene is likely a subunit of the 13S condensin complex, which is involved in chromosome condensation. A pseudogene related to this gene is located on chromosome 2. [provided by RefSeq, Jun 2016]

OMIM Research

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

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.48

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.48LOEUF

pLI 0.000

Z-score 4.81

OE 0.33 (0.23–0.48)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.08Z-score

OE missense 0.88 (0.82–0.94)

574 obs / 651.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.33 (0.23–0.48)

0≤0.351.4

Missense OE?0.88 (0.82–0.94)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 20 / 60.3Missense obs/exp: 574 / 651.5Syn Z: -1.60

Background carrier burden — how many people carry a rare variant somewhere in SMC4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 48

1,534 rare PASS variants

Rare truncating (LoF)

1 in 270

307 rare PASS variants

Rare synonymous (reference)

1 in 79

589 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SMC4. 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 74	1 in 380
South Asian	~43k	1 in 40	1 in 270
Remaining (unassigned)	~30k	1 in 42	1 in 240
European (Finnish)	~27k	1 in 140	1 in 1,400
Admixed American	~22k	1 in 43	1 in 150
African / African American	~21k	1 in 43	1 in 190
East Asian	~20k	1 in 63	1 in 190
Ashkenazi Jewish	~13k	1 in 170	1 in 330
Middle Eastern	~2,884	1 in 40	1 in 270

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 17 of 23 coding exons well covered in gnomAD exomes; exons 2, 3, 7, 8, 10, 24 marginal. Genomes: all 23.? see exons ↓