SPCS1

protein-coding

signal peptidase complex subunit 1

Gene summary

Predicted to enable ribosome binding activity. Involved in obsolete signal peptide processing; viral protein processing; and virion assembly. Located in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_014041.5

Inheritance

—

ClinVar variants

U:14

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.49

Max pathogenic AF

—

Genomic locus

chr3:52,704,955-52,711,148

External References & Databases

Ensembl (ENSG00000114902)

Transcript & Mutation Effects

hg38 • Region Span ~6.2 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 SPCS1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 11

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014041.5. 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			11 clinvar			11
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	14	0	0	14

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014041.5	RefSeq	NP_054760.4	4	MANE Select
ENST00000619898.5	Ensembl	ENSP00000478310.2	4	MANE Select
ENST00000233025.11	Ensembl	ENSP00000233025.7	4	Standard
ENST00000233025.12	Ensembl	ENSP00000233025.7	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Protein export - Homo sapiens (human)
Biotin Metabolism
Multiple carboxylase deficiency, neonatal or early onset form
Biotinidase Deficiency
Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP)

Biological Process

signal peptide processing
proteolysis
protein targeting to ER

Molecular Function

molecular_function
protein binding
peptidase activity

Cellular Component

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

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000233025
Coding exons: 4
Length: 3212
Individuals with no LoFs: 125743
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 125748
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.462	85	97.9	0.869	0.00000476	1054
Missense (PolyPhen)		17	26.537	0.64061		317
Synonymous	0.466	37	40.8	0.907	0.00000205	348
Loss of Function	1.34	4	8.11	0.493	3.45e-7	91

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	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000035	rare
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 from nascent proteins as they are translocated into the lumen of the endoplasmic reticulum. {ECO:0000250}.;

Recessive Scores

pRec: 0.116

Intolerance Scores

LoFtool: 0.495
RVIS EVS: 0.3
RVIS percentile EVS: 71.81

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.952

Gene Damage Prediction

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