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…

DNmechanismLOEUF 0.48

Clinical Summary— SMC4

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.

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ClinVar Variants

152 VUS of 196 total submissions

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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

This gene — mechanism propensity

0.7036th %ile

GOF

0.5954th %ile

LOF

0.2385th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

196 submitted variants in ClinVar

ClinVar

Classification Summary

VUS152

Likely Benign7

Benign3

152

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	149	1	1	152
Likely Benign	0	4	2	1	7
Benign	0	1	2	0	3
Total	1	154	5	2	162

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

21 pathogenic / likely-pathogenic (of 24) ClinVar copy-number / structural variants overlap SMC4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →