SIMC1

Chr 5

SUMO interacting motifs containing 1

Also known as: C5orf25, OOMA1, PLEIAD

NCBI Gene: 375484 ENSG00000170085 UniProt: Q8NDZ2 OMIM: 618102

SIMC1 encodes a protein that enables SUMO polymer binding and peptidase inhibitor activity, and forms complexes required to recruit the SMC5-SMC6 complex to PML nuclear bodies for viral restriction. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, seizures, and progressive brain atrophy. The gene shows high constraint against loss-of-function variants, indicating intolerance to protein-truncating mutations.

OMIM ResearchSummary from RefSeq, UniProt

Enables SUMO polymer binding activity and peptidase inhibitor activity. Located in PML body and sarcomere. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.91

Clinical Summary— SIMC1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

74 VUS of 89 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.91LOEUF

pLI 0.000

Z-score 1.87

OE 0.56 (0.36–0.91)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.54Z-score

OE missense 0.90 (0.80–1.01)

202 obs / 224.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.56 (0.36–0.91)

0≤0.351.4

Missense OE?0.90 (0.80–1.01)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 12 / 21.3Missense obs/exp: 202 / 224.6Syn Z: 0.08

ClinVar Variant Classifications

89 submitted variants in ClinVar

ClinVar

Classification Summary

VUS74

Likely Benign4

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	74	0	0	74
Likely Benign	2	1	1	4
Benign	0	0	1	1
Total	76	1	2	79

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

View in ClinVar →

47 pathogenic / likely-pathogenic (of 55) ClinVar copy-number / structural variants overlap SIMC1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →