PTPN14

protein-coding

protein tyrosine phosphatase non-receptor type 14, the group of FERM domain containing|Protein tyrosine phosphatases non-receptor type

Gene summary

The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains an N-terminal noncatalytic domain similar to that of band 4.1 superfamily cytoskeleton-associated proteins, which suggested the membrane or cytoskeleton localization of this protein. It appears to regulate lymphatic development in mammals, and a loss of function mutation has been found in a kindred with a lymphedema-choanal atresia. [provided by RefSeq, Sep 2010]

MANE transcript

NM_005401.5

Inheritance

ClinVar variants

P:4U:167B:41

Top phenotype

Choanal atresia and lymphedema

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chr1:214,348,700-214,552,449

External References & Databases

Ensembl (ENSG00000152104)

Transcript & Mutation Effects

hg38 • Region Span ~203.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

lymphedema-posterior choanal atresia syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0013324

Submitter: Ambry Genetics

lymphedema-posterior choanal atresia syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013324

Submitter: Labcorp Genetics (formerly Invitae)

lymphedema-posterior choanal atresia syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013324

Submitter: G2P

lymphedema-posterior choanal atresia syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013324

Submitter: Orphanet

lymphedema-posterior choanal atresia syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013324

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Choanal atresia and lymphedemaAR

Manifestation: Audiologic/Otolaryngologic; Cardiovascular; Craniofacial

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: 7158640; 1872518; 20826270

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PTPN14 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 155

not providedTotal: 39

Lymphedema-posterior choanal atresia syndromeTotal: 24

PTPN14-related disorderTotal: 13

Esophageal atresia/tracheoesophageal fistulaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005401.5. 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			2 clinvar	24 clinvar	5 clinvar	31
missense		1 clinvar	155 clinvar	9 clinvar	3 clinvar	168
nonsense	1 clinvar		3 clinvar			4
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)	1 clinvar		7 clinvar			8
Total	3	1	167	33	8	212

Highest pathogenic variant AF is 0.000008898588

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005401.5	RefSeq	NP_005392.2	18	MANE Select
ENST00000366956.10	Ensembl	ENSP00000355923.4	18	MANE Select
ENST00000543945.5	Ensembl	ENSP00000443330.1	6	Standard
ENST00000543945.6	Ensembl	ENSP00000443330.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

lymphangiogenesis
protein dephosphorylation
negative regulation of cell population proliferation
peptidyl-tyrosine dephosphorylation
regulation of protein export from nucleus

Molecular Function

transcription coregulator activity
protein tyrosine phosphatase activity
protein binding
receptor tyrosine kinase binding

Cellular Component

nucleus
nucleoplasm
cytoplasm
cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000366956
Coding exons: 18
Length: 203754
Individuals with no LoFs: 125725
Homozygous LoFs: 0
Heterozygous LoFs: 23
Defined: 125748
p: 0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.68	591	718	0.824	0.0000440	7814
Missense (PolyPhen)		202	298	0.67785		3210
Synonymous	-0.395	299	290	1.03	0.0000197	2298
Loss of Function	5.50	14	59.9	0.234	0.00000367	623

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000055	0.000054	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.000088	0.000088	rare
South Asian	0.000098	0.000098	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Protein tyrosine phosphatase which may play a role in the regulation of lymphangiogenesis, cell-cell adhesion, cell- matrix adhesion, cell migration, cell growth and also regulates TGF-beta gene expression, thereby modulating epithelial- mesenchymal transition. Mediates beta-catenin dephosphorylation at adhesion junctions. Acts as a negative regulator of the oncogenic property of YAP, a downstream target of the hippo pathway, in a cell density-dependent manner. May function as a tumor suppressor. {ECO:0000269|PubMed:10934049, ECO:0000269|PubMed:12808048, ECO:0000269|PubMed:17893246, ECO:0000269|PubMed:20826270, ECO:0000269|PubMed:22233626, ECO:0000269|PubMed:22525271, ECO:0000269|PubMed:22948661}.;
Disease: DISEASE: Choanal atresia and lymphedema (CATLPH) [MIM:613611]: A disease characterized by posterior choanal atresia and lymphedema. Additional features are a high-arched palate, hypoplastic nipples, and mild pectus excavatum. {ECO:0000269|PubMed:20826270}. Note=The disease is caused by mutations affecting the gene represented in this entry. A homozygous deletion in PTPN14 predicted to result in frameshift and premature truncation, has been shown to be the cause of choanal atresia and lymphedema in one family.; DISEASE: Note=Influence clinical severity of hereditary haemorragic telagiectasia (HHT). {ECO:0000269|PubMed:22233626}.;

Recessive Scores

pRec: 0.283

Intolerance Scores

LoFtool: 0.166
RVIS EVS: -0.3
RVIS percentile EVS: 32.28

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.902

Gene Damage Prediction

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