SIMC1

protein-coding

SUMO interacting motifs containing 1

Gene summary

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

Previous symbols:

C5orf25

MANE transcript

NM_001308195.2

Inheritance

—

ClinVar variants

U:80B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.56

Max pathogenic AF

—

Genomic locus

chr5:176,238,367-176,345,991

External References & Databases

Ensembl (ENSG00000170085)

Transcript & Mutation Effects

hg38 • Region Span ~107.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SIMC1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 76

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001308195.2. 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			1 clinvar	1 clinvar	1 clinvar	3
missense			75 clinvar	2 clinvar		77
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	80	3	1	84

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 39 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001308195.2	RefSeq	NP_001295124.1	10	MANE Select
ENST00000429602.7	Ensembl	ENSP00000410552.3	10	MANE Select
NM_001308196.2	RefSeq	NP_001295125.1	10	Standard
NM_001308200.2	RefSeq	NP_001295129.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

SUMO polymer binding

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000341199
Coding exons: 9
Length: 107630
Individuals with no LoFs: 125539
Homozygous LoFs: 0
Heterozygous LoFs: 53
Defined: 125592
p: 0.000211

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.536	202	225	0.899	0.0000116	2979
Missense (PolyPhen)		67	84.982	0.7884		1091
Synonymous	0.0846	85	86.0	0.988	0.00000467	884
Loss of Function	1.87	12	21.3	0.563	0.00000114	243

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.00040	0.00040	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0820

Intolerance Scores

RVIS EVS: -0.58
RVIS percentile EVS: 18.59

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N

Gene Damage Prediction

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