SPRR2A

protein-coding

small proline rich protein 2A, the group of Small proline rich proteins

Gene summary

Enables lipid binding activity. Involved in antibacterial humoral response and defense response to Gram-positive bacterium. Located in cytoplasm. Is active in extracellular region and secretory granule. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_005988.3

Inheritance

—

ClinVar variants

U:8B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e —

Max pathogenic AF

—

Genomic locus

chr1:153,056,120-153,057,512

External References & Databases

Ensembl (ENSG00000241794)

Transcript & Mutation Effects

hg38 • Region Span ~1.4 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 SPRR2A variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 9

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005988.3. 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			8 clinvar	1 clinvar	1 clinvar	10
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	8	1	1	10

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005988.3	RefSeq	NP_005979.1	1	MANE Select
ENST00000392653.3	Ensembl	ENSP00000376423.2	1	MANE Select
ENST00001096805.1	Ensembl	ENSP00000766611.1	1	Standard
ENST00001096806.1	Ensembl	ENSP00000766612.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Keratinization
Developmental Biology
Formation of the cornified envelope

Biological Process

epidermis development
peptide cross-linking
keratinocyte differentiation
cornification

Molecular Function

structural molecule activity
protein binding

Cellular Component

cornified envelope
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000392653
Coding exons: 1
Length: 1425

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.430	47	39.4	1.19	0.00000196	456
Missense (PolyPhen)
Synonymous	-0.463	18	15.7	1.15	8.94e-7	135
Loss of Function

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: Cross-linked envelope protein of keratinocytes. It is a keratinocyte protein that first appears in the cell cytosol, but ultimately becomes cross-linked to membrane proteins by transglutaminase. All that results in the formation of an insoluble envelope beneath the plasma membrane.;

Intolerance Scores

LoFtool: 0.591
RVIS EVS: 0.32
RVIS percentile EVS: 72.94

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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