PTPN14

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

Basic information

Region (hg38): 1:214348699-214552449

Links

ENSG00000152104 ∙ NCBI:5784 ∙ OMIM:603155 ∙ HGNC:9647 ∙ Uniprot:Q15678 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• lymphedema-posterior choanal atresia syndrome (Supportive), mode of inheritance: AR
• lymphedema-posterior choanal atresia syndrome (Strong), mode of inheritance: AR
• lymphedema-posterior choanal atresia syndrome (Strong), mode of inheritance: AR
• lymphedema-posterior choanal atresia syndrome (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Choanal atresia and lymphedema	AR	General	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	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial	7158640; 1872518; 20826270

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PTPN14 gene.

• not provided (82 variants)
• Inborn genetic diseases (34 variants)
• Lymphedema-posterior choanal atresia syndrome (16 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PTPN14 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				12	9	21
missense			37	3	5	45
nonsense	1		1			2
start loss						0
frameshift						0
inframe indel					1	1
splice donor/acceptor (+/-2bp)						0
splice region			1		4	5
non coding			3	1	45	49
Total	1	0	41	16	60

Highest pathogenic variant AF is 0.0000592

Variants in PTPN14

This is a list of pathogenic ClinVar variants found in the PTPN14 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-214351602-G-A		Lymphedema-posterior choanal atresia syndrome	Uncertain significance (Nov 22, 2021)
1-214357735-GA-G			Benign (Nov 12, 2018)
1-214357896-C-T		Lymphedema-posterior choanal atresia syndrome	Benign (Nov 07, 2021)
1-214357986-A-G		Lymphedema-posterior choanal atresia syndrome • not specified	Uncertain significance (Sep 15, 2023)
1-214364206-C-T			Benign (Nov 12, 2018)
1-214364284-C-T			Benign (Jun 19, 2021)
1-214364515-G-A			Likely benign (Jun 29, 2018)
1-214364544-C-T		not specified	Uncertain significance (Jul 06, 2021)
1-214364603-G-A			Benign (Dec 31, 2019)
1-214364609-C-T		not specified	Uncertain significance (Nov 18, 2023)
1-214364635-G-A			Benign (Dec 31, 2019)
1-214364636-T-C		not specified	Uncertain significance (Dec 14, 2021)
1-214364943-A-T			Benign (Nov 12, 2018)
1-214369325-T-C			Benign (Nov 12, 2018)
1-214369476-T-C		Lymphedema-posterior choanal atresia syndrome	Benign (Nov 07, 2021)
1-214369548-G-A			Benign (Dec 31, 2019)
1-214369590-C-T			Likely benign (Jun 23, 2018)
1-214369591-G-C			Likely benign (Dec 01, 2023)
1-214369674-T-G		not specified	Uncertain significance (Jan 23, 2024)
1-214369682-G-A			Pathogenic (Jul 05, 2022)
1-214369755-A-G			Benign (Nov 12, 2018)
1-214372417-T-G			Benign (Jun 19, 2021)
1-214373141-G-A			Benign (Nov 12, 2018)
1-214376158-C-T			Benign (Jun 20, 2021)
1-214376267-T-C		not specified	Uncertain significance (Aug 02, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PTPN14	protein_coding	protein_coding	ENST00000366956	18	203754

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.221	0.779	125725	0	23	125748	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.68	591	718	0.824	0.0000440	7814
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000218	0.000213
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000550	0.0000544
Finnish	0.000139	0.000139
European (Non-Finnish)	0.0000884	0.0000879
Middle Eastern	0.0000550	0.0000544
South Asian	0.0000980	0.0000980
Other	0.000326	0.000326

dbNSFP

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

Haploinsufficiency Scores

• pHI: 0.251
• hipred: Y
• hipred_score: 0.563
• ghis: 0.491

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.902

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ptpn14
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; vision/eye phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); immune system phenotype

Gene ontology

• Biological process: lymphangiogenesis;protein dephosphorylation;negative regulation of cell population proliferation;peptidyl-tyrosine dephosphorylation;regulation of protein export from nucleus;cellular response to cytokine stimulus;regulation of nucleic acid-templated transcription
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytoskeleton
• Molecular function: transcription coregulator activity;protein tyrosine phosphatase activity;protein binding;receptor tyrosine kinase binding