SPCS2

protein-coding

signal peptidase complex subunit 2

Gene summary

Predicted to enable peptidase activity. Involved in obsolete signal peptide processing. Located in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_014752.3

Inheritance

—

ClinVar variants

U:18B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr11:74,949,261-74,979,033

External References & Databases

Ensembl (ENSG00000118363)

Transcript & Mutation Effects

hg38 • Region Span ~29.8 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 SPCS2 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 19

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014752.3. 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			18 clinvar	1 clinvar		19
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	18	1	0	19

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014752.3	RefSeq	NP_055567.2	5	MANE Select
ENST00000263672.11	Ensembl	ENSP00000263672.6	5	MANE Select
ENST00000526361.1	Ensembl	ENSP00000434248.1	3	Standard
ENST00000526361.2	Ensembl	ENSP00000434248.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Protein export - Homo sapiens (human)
Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP)
Incretin synthesis, secretion, and inactivation
Peptide hormone metabolism
SRP-dependent cotranslational protein targeting to membrane

Biological Process

signal peptide processing
protein targeting to ER

Molecular Function

peptidase activity

Cellular Component

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: ENST00000263672
Coding exons: 5
Length: 29785
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	1.42	75	119	0.632	0.00000557	1496
Missense (PolyPhen)		6	31.483	0.19058		465
Synonymous	0.395	39	42.3	0.923	0.00000207	419
Loss of Function	2.69	0	8.43	0.00	3.53e-7	120

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 from nascent proteins as they are translocated into the lumen of the endoplasmic reticulum. {ECO:0000250}.;

Recessive Scores

pRec: 0.118

Intolerance Scores

LoFtool: 0.222
RVIS EVS: 0.01
RVIS percentile EVS: 54.63

Essentials

Essential (CRISPR): N
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.743

Gene Damage Prediction

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