SH3PXD2B

SH3 and PX domains 2B

Basic information

Region (hg38): 5:172325000-172454525

Previous symbols: [ "KIAA1295" ]

Links

ENSG00000174705 ∙ NCBI:285590 ∙ OMIM:613293 ∙ HGNC:29242 ∙ Uniprot:A1X283 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Frank-Ter Haar syndrome (Definitive), mode of inheritance: AR
• Frank-Ter Haar syndrome (Strong), mode of inheritance: AR
• Frank-Ter Haar syndrome (Strong), mode of inheritance: AR
• Frank-Ter Haar syndrome (Supportive), mode of inheritance: AR
• Frank-Ter Haar syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Frank-ter Haar syndrome	AR	Cardiovascular; Ophthalmologic; Pharmacogenomic	The condition may be clinically recognizable, but can include macrocornea with or without glaucoma, and surveillance and prompt treatment may be beneficial; Awareness of cardiac anomalies may allow prompt management; Agents that may contribute to glaucoma should be avoided	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	4805907; 7158646; 9375925; 9188664; 15523657; 20137777; 24105366

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SH3PXD2B gene.

• not provided (3 variants)
• Frank-Ter Haar syndrome (1 variants)
• SH3PXD2B-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SH3PXD2B 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			2	74	8	84
missense		1	156	16	5	178
nonsense	1	1	2			4
start loss						0
frameshift	3	1	3			7
inframe indel			5	1		6
splice donor/acceptor (+/-2bp)		1				1
splice region			2	7	2	11
non coding			82	59	73	214
Total	4	4	250	150	86

Highest pathogenic variant AF is 0.00000657

Variants in SH3PXD2B

This is a list of pathogenic ClinVar variants found in the SH3PXD2B region.

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

Position	Type	Phenotype	Significance	ClinVar
5-172325268-C-G		SH3PXD2B-related disorder	Likely benign (Jun 05, 2020)
5-172325312-T-C		SH3PXD2B-related disorder	Likely benign (Feb 04, 2021)
5-172333540-TA-T		Frank-Ter Haar syndrome	Benign (Jun 14, 2016)
5-172333540-T-TA		Frank-Ter Haar syndrome	Uncertain significance (Jun 14, 2016)
5-172333541-A-T		Frank-Ter Haar syndrome	Benign (Jan 12, 2018)
5-172333542-A-T		Frank-Ter Haar syndrome	Benign (Jan 12, 2018)
5-172333564-C-T		Frank-Ter Haar syndrome	Uncertain significance (Jan 12, 2018)
5-172333565-A-G		Frank-Ter Haar syndrome	Benign (Jan 12, 2018)
5-172333596-C-G		Frank-Ter Haar syndrome	Uncertain significance (Jan 15, 2018)
5-172333633-T-C		Frank-Ter Haar syndrome	Uncertain significance (Jan 12, 2018)
5-172333676-G-A		Frank-Ter Haar syndrome	Uncertain significance (Jan 12, 2018)
5-172333700-AGAGT-A		Frank-Ter Haar syndrome	Uncertain significance (Jun 14, 2016)
5-172333808-C-T		Frank-Ter Haar syndrome	Uncertain significance (Jan 12, 2018)
5-172333880-G-A		Frank-Ter Haar syndrome	Uncertain significance (Jan 12, 2018)
5-172333949-T-C		Frank-Ter Haar syndrome	Uncertain significance (Jan 13, 2018)
5-172334041-G-A		Frank-Ter Haar syndrome	Uncertain significance (Jan 12, 2018)
5-172334086-C-T		Frank-Ter Haar syndrome	Uncertain significance (Jan 12, 2018)
5-172334103-C-A		Frank-Ter Haar syndrome	Uncertain significance (Jan 13, 2018)
5-172334267-C-A		Frank-Ter Haar syndrome	Uncertain significance (Jan 12, 2018)
5-172334290-G-A		Frank-Ter Haar syndrome	Uncertain significance (Jan 13, 2018)
5-172334334-C-T		Frank-Ter Haar syndrome	Benign (Jan 13, 2018)
5-172334380-C-T		Frank-Ter Haar syndrome	Likely benign (Jan 13, 2018)
5-172334433-C-T		Frank-Ter Haar syndrome	Benign (Jan 13, 2018)
5-172334434-G-A		Frank-Ter Haar syndrome	Uncertain significance (Jan 13, 2018)
5-172334511-C-G		Frank-Ter Haar syndrome	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SH3PXD2B	protein_coding	protein_coding	ENST00000311601	13	129343

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00416	0.996	125568	0	180	125748	0.000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.526	511	546	0.937	0.0000347	5925
Missense in Polyphen		159	204.39	0.77791		2252
Synonymous	0.830	213	229	0.930	0.0000162	1817
Loss of Function	4.08	12	39.8	0.301	0.00000198	465

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000702	0.000698
Ashkenazi Jewish	0.00566	0.00567
East Asian	0.000164	0.000163
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000555	0.000554
Middle Eastern	0.000164	0.000163
South Asian	0.000555	0.000555
Other	0.00212	0.00212

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Adapter protein involved in invadopodia and podosome formation and extracellular matrix degradation. Binds matrix metalloproteinases (ADAMs), NADPH oxidases (NOXs) and phosphoinositides. Acts as an organizer protein that allows NOX1- or NOX3-dependent reactive oxygen species (ROS) generation and ROS localization. Plays a role in mitotic clonal expansion during the immediate early stage of adipocyte differentiation (By similarity). {ECO:0000250, ECO:0000269|PubMed:12615925, ECO:0000269|PubMed:19755710, ECO:0000269|PubMed:20609497}.
• Disease: DISEASE: Frank-Ter Haar syndrome (FTHS) [MIM:249420]: A syndrome characterized by brachycephaly, wide fontanels, prominent forehead, hypertelorism, prominent eyes, macrocornea with or without glaucoma, full cheeks, small chin, bowing of the long bones and flexion deformity of the fingers. {ECO:0000269|PubMed:20137777}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.105

Intolerance Scores

• loftool: 0.628
• rvis_EVS: -0.28
• rvis_percentile_EVS: 33.57

Haploinsufficiency Scores

• pHI: 0.262
• hipred: N
• hipred_score: 0.462
• ghis: 0.556

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.128

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sh3pxd2b
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); muscle phenotype; vision/eye phenotype; craniofacial phenotype; reproductive system 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); immune system phenotype; skeleton phenotype; hearing/vestibular/ear phenotype; limbs/digits/tail phenotype

Gene ontology

• Biological process: skeletal system development;eye development;osteoblast fate commitment;superoxide metabolic process;heart development;positive regulation of gene expression;extracellular matrix disassembly;positive regulation of multicellular organism growth;positive regulation of catalytic activity;positive regulation of fat cell differentiation;skeletal system morphogenesis;positive regulation of stress fiber assembly;bone development;regulation of brood size;adipose tissue development;podosome assembly;protein localization to membrane;positive regulation of adipose tissue development;cranial skeletal system development
• Cellular component: podosome;cytoplasm;cell junction;cell projection
• Molecular function: protein binding;phosphatidylinositol-5-phosphate binding;superoxide-generating NADPH oxidase activator activity;phosphatidylinositol-3-phosphate binding;phosphatidylinositol binding;SH2 domain binding;phosphatidylinositol-4-phosphate binding;phosphatidylinositol-3,5-bisphosphate binding