PRRG4

protein-coding

proline rich and Gla domain 4, the group of Proline rich and Gla domain containing

Gene summary

Enables WW domain binding activity. Predicted to be involved in blood coagulation and proteolysis. Located in plasma membrane. Biomarker of cholangiocarcinoma. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_024081.6

Inheritance

—

ClinVar variants

U:21B:4

Top phenotype

PRRG4-related disorder

gnomAD constraint

pLI —, LoF o/e 0.32

Max pathogenic AF

—

Genomic locus

chr11:32,829,927-32,858,120

External References & Databases

Ensembl (ENSG00000135378)

Transcript & Mutation Effects

hg38 • Region Span ~28.2 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 PRRG4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 22

PRRG4-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024081.6. 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			20 clinvar	4 clinvar		24
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	21	4	0	25

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024081.6	RefSeq	NP_076986.1	5	MANE Select
ENST00000257836.4	Ensembl	ENSP00000257836.3	5	MANE Select
ENST00000867854.1	Ensembl	ENSP00000537913.1	5	Standard
ENST00000867854.2	Ensembl	ENSP00000537913.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Glucocorticoid Receptor Pathway
Nuclear Receptors Meta-Pathway

Biological Process

biological_process

Molecular Function

molecular_function
calcium ion binding

Cellular Component

extracellular region
integral component of membrane
endoplasmic reticulum-Golgi intermediate compartment membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000257836
Coding exons: 5
Length: 28181
Individuals with no LoFs: 125740
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125748
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.31	78	118	0.660	0.00000574	1439
Missense (PolyPhen)		15	33.251	0.45112		431
Synonymous	0.933	37	45.0	0.823	0.00000223	454
Loss of Function	1.92	3	9.34	0.321	3.88e-7	138

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	0.000055	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.00010	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May control axon guidance across the CNS (PubMed:28859078). Prevents the delivery of ROBO1 at the cell surface and downregulates its expression (PubMed:28859078). {ECO:0000269|PubMed:28859078}.;

Recessive Scores

pRec: 0.0784

Intolerance Scores

LoFtool: 0.216
RVIS EVS: 1.08
RVIS percentile EVS: 91.8

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0549

Gene Damage Prediction

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