SPCS3

protein-coding

signal peptidase complex subunit 3

Gene summary

Involved in obsolete signal peptide processing and viral protein processing. Located in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_021928.4

Inheritance

—

ClinVar variants

U:15

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr4:176,319,966-176,332,245

External References & Databases

Ensembl (ENSG00000129128)

Transcript & Mutation Effects

hg38 • Region Span ~12.3 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 SPCS3 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 12

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021928.4. 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						0
missense			13 clinvar			13
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	15	0	0	15

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021928.4	RefSeq	NP_068747.1	5	MANE Select
ENST00000503362.2	Ensembl	ENSP00000427463.1	5	MANE Select
ENST00001044112.1	Ensembl	ENSP00000713929.1	1	Standard
ENST00001121319.1	Ensembl	ENSP00000791124.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Protein export - Homo sapiens (human)
miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in muscle cell - TarBase
miR-targeted genes in squamous cell - TarBase
Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP)

Biological Process

signal peptide processing
proteolysis
protein targeting to ER

Molecular Function

peptidase activity

Cellular Component

endoplasmic reticulum
signal peptidase complex
endoplasmic reticulum membrane
integral component of membrane
organelle membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000503362
Coding exons: 5
Length: 12282
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.04	35	89.2	0.392	0.00000433	1153
Missense (PolyPhen)		4	24.742	0.16167		387
Synonymous	0.359	36	38.8	0.927	0.00000215	350
Loss of Function	2.20	0	5.66	0.00	2.36e-7	94

Population LoF Frequency

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

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the microsomal signal peptidase complex which removes signal peptides and other N-terminal peptides from nascent proteins as they are translocated into the lumen of the endoplasmic reticulum. {ECO:0000269|PubMed:27499293}.;

Recessive Scores

pRec: 0.108

Intolerance Scores

RVIS EVS: 0.01
RVIS percentile EVS: 54.63

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: N
Indispensability score: 0.267

Gene Damage Prediction

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