PRRG1

protein-coding

proline rich and Gla domain 1, the group of Proline rich and Gla domain containing

Gene summary

This gene encodes a vitamin K-dependent, gamma-carboxyglutamic acid (Gla)-containing, single-pass transmembrane protein. This protein contains a Gla domain at the N-terminus, preceded by a propeptide sequence required for post-translational gamma-carboxylation of specific glutamic acid residues by a vitamin K-dependent gamma-carboxylase. The C-terminus is proline-rich containing PPXY and PXXP motifs found in a variety of signaling and cytoskeletal proteins. This gene is highly expressed in the spinal cord. Several alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2010]

MANE transcript

NM_001142395.2

Inheritance

—

ClinVar variants

U:45B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.36

Max pathogenic AF

—

Genomic locus

chrX:37,349,309-37,492,702

External References & Databases

Ensembl (ENSG00000130962)

Transcript & Mutation Effects

hg38 • Region Span ~143.4 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 PRRG1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 21

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001142395.2. 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			7 clinvar	1 clinvar		8
missense			31 clinvar	1 clinvar		32
nonsense			2 clinvar			2
start loss			1 clinvar			1
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	45	2	0	47

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 43 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001142395.2	RefSeq	NP_001135867.1	3	MANE Select
ENST00000378628.9	Ensembl	ENSP00000367894.4	3	MANE Select
NM_000950.3	RefSeq	NP_000941.1	3	Standard
NM_001173486.2	RefSeq	NP_001166957.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

calcium ion binding

Cellular Component

extracellular region
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000542554
Coding exons: 3
Length: 108021
Individuals with no LoFs: 125734
Homozygous LoFs: 3
Heterozygous LoFs: 5
Defined: 125742
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.409	71	81.4	0.873	0.00000628	1437
Missense (PolyPhen)		14	21.634	0.64714		431
Synonymous	-0.596	34	29.9	1.14	0.00000226	421
Loss of Function	1.40	2	5.58	0.358	4.22e-7	104

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000076	0.000062	rare
Latino/Admixed American	0.000037	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000063	0.000046	rare
European (Non-Finnish)	0.000063	0.000044	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.121

Intolerance Scores

LoFtool: 0.238
RVIS EVS: 0.08
RVIS percentile EVS: 59.76

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.175

Gene Damage Prediction

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