PITPNM3

protein-coding

PITPNM family member 3, the group of Atypical chemokine receptors|Phosphatidylinositol transfer proteins

Gene summary

This gene encodes a member of a family of membrane-associated phosphatidylinositol transfer domain-containing proteins. The calcium-binding protein has phosphatidylinositol (PI) transfer activity and interacts with the protein tyrosine kinase PTK2B (also known as PYK2). The protein is homologous to a Drosophila protein that is implicated in the visual transduction pathway in flies. Mutations in this gene result in autosomal dominant cone dystrophy. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

Previous symbols:

CORD5

MANE transcript

NM_031220.4

Inheritance

ClinVar variants

P:4U:452B:305

Top phenotype

Cone-rod dystrophy 5

gnomAD constraint

pLI —, LoF o/e 0.09

Max pathogenic AF

—

Genomic locus

chr17:6,451,263-6,556,555

External References & Databases

Ensembl (ENSG00000091622)

Transcript & Mutation Effects

hg38 • Region Span ~105.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cone-rod dystrophy 5STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0010969

Submitter: Labcorp Genetics (formerly Invitae)

cone-rod dystrophy 5LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0010969

Submitter: G2P

cone-rod dystrophySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0015993

Submitter: Orphanet

Clinical Genomic Database (CGD)

Cone-rod dystrophy 5AD

Manifestation: Ophthalmologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 8586428; 17377520; 18188949; 22405330

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PITPNM3 variants in ClinVar

8 Conditions Cataloged

not providedTotal: 867

not specifiedTotal: 331

Cone-rod dystrophy 5Total: 66

PITPNM3-related disorderTotal: 23

Retinal dystrophyTotal: 9

Retinitis pigmentosaTotal: 3

Cone dystrophyTotal: 1

Cerebral arteriovenous malformationTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_031220.4. 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			8 clinvar	262 clinvar	1 clinvar	271
missense			431 clinvar	42 clinvar		473
nonsense	2 clinvar	1 clinvar	4 clinvar			7
start loss						0
frameshift	1 clinvar		2 clinvar			3
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	3	1	452	304	1	761

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_031220.4	RefSeq	NP_112497.2	20	MANE Select
ENST00000262483.13	Ensembl	ENSP00000262483.8	20	MANE Select
NM_001165966.2	RefSeq	NP_001159438.1	19	Standard
ENST00000421306.7	Ensembl	ENSP00000407882.3	19	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metabolism of lipids
Metabolism
Synthesis of PI
Glycerophospholipid biosynthesis
Phospholipid metabolism

Biological Process

phosphatidylinositol biosynthetic process
endoplasmic reticulum to Golgi vesicle-mediated transport
phospholipid transport

Molecular Function

phospholipase activity
calcium ion binding
protein binding
lipid binding
phosphatidylinositol transporter activity

Cellular Component

cytosol
endomembrane system
membrane
COPII-coated ER to Golgi transport vesicle
cell projection

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000262483
Coding exons: 20
Length: 105231
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 15
Defined: 125748
p: 0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.01	460	599	0.768	0.0000399	6334
Missense (PolyPhen)		84	151.07	0.55602		1616
Synonymous	-0.777	279	263	1.06	0.0000186	1975
Loss of Function	5.63	4	44.5	0.0899	0.00000239	482

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000060	0.000058	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000080	0.000079	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the transfer of phosphatidylinositol and phosphatidylcholine between membranes (in vitro) (By similarity). Binds calcium ions. {ECO:0000250}.;

Recessive Scores

pRec: 0.111

Intolerance Scores

LoFtool: 0.0640
RVIS EVS: -1.39
RVIS percentile EVS: 4.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.456

Gene Damage Prediction

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