SH3PXD2B

Summary

SH3PXD2B (SH3 and PX domains 2B, HGNC:29242) is a protein-coding gene on chromosome 5q35.1, encoding SH3 and PX domain-containing protein 2B (A1X283). Adapter protein involved in invadopodia and podosome formation and extracellular matrix degradation.

This gene encodes an adapter protein that is characterized by a PX domain and four Src homology 3 domains. The encoded protein is required for podosome formation and is involved in cell adhesion and migration of numerous cell types. Mutations in this gene are the cause of Frank-ter Haar syndrome (FTHS), and also Borrone Dermato-Cardio-Skeletal (BDCS) syndrome. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 285590 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Frank-Ter Haar syndrome (Definitive, ClinGen)
• GWAS associations: 10
• Clinical variants (ClinVar): 680 total — 10 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 86
• MANE Select transcript: NM_001017995

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29242
Approved symbol	SH3PXD2B
Name	SH3 and PX domains 2B
Location	5q35.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20831
Ensembl gene	ENSG00000174705
Ensembl biotype	protein_coding
OMIM	613293
Entrez	285590

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000311601, ENST00000518522, ENST00000519643, ENST00000523651, ENST00000636523, ENST00000918640, ENST00000918641, ENST00000971124

RefSeq mRNA: 2 — MANE Select: NM_001017995 NM_001017995, NM_001308175

CCDS: CCDS34291, CCDS78084

Canonical transcript exons

ENST00000311601 — 13 exons

Exon	Start	End
ENSE00001223292	172333499	172339916
ENSE00001364389	172350363	172350589
ENSE00001375110	172347283	172347332
ENSE00001376855	172422416	172422496
ENSE00001378384	172353888	172354005
ENSE00001381933	172362735	172362869
ENSE00001384794	172382036	172382127
ENSE00001385545	172394563	172394639
ENSE00001385663	172373790	172373815
ENSE00001387642	172346136	172346261
ENSE00001391665	172358773	172358877
ENSE00001430210	172454278	172454525
ENSE00002527001	172406277	172406352

Expression profiles

Bgee: expression breadth ubiquitous, 224 present calls, max score 96.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.6092 / max 132.1101, expressed in 1609 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
64872	16.0527	1587
64870	1.1976	720
64871	0.6697	443
64868	0.4533	254
64869	0.2359	98

Top tissues by expression

254 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
decidua	UBERON:0002450	96.33	gold quality
sural nerve	UBERON:0015488	92.58	gold quality
urethra	UBERON:0000057	92.12	gold quality
skin of hip	UBERON:0001554	91.96	gold quality
adrenal tissue	UBERON:0018303	91.94	gold quality
nasal cavity epithelium	UBERON:0005384	91.80	silver quality
ventricular zone	UBERON:0003053	91.28	gold quality
endocervix	UBERON:0000458	90.17	gold quality
mucosa of stomach	UBERON:0001199	89.72	gold quality
uterine cervix	UBERON:0000002	89.68	gold quality
myometrium	UBERON:0001296	89.64	gold quality
stromal cell of endometrium	CL:0002255	89.29	gold quality
upper arm skin	UBERON:0004263	89.18	silver quality
saphenous vein	UBERON:0007318	88.55	gold quality
ectocervix	UBERON:0012249	88.44	gold quality
cortical plate	UBERON:0005343	88.37	gold quality
smooth muscle tissue	UBERON:0001135	88.32	gold quality
left adrenal gland cortex	UBERON:0035825	88.27	gold quality
left uterine tube	UBERON:0001303	88.15	gold quality
left adrenal gland	UBERON:0001234	87.92	gold quality
ganglionic eminence	UBERON:0004023	87.78	gold quality
embryo	UBERON:0000922	87.77	gold quality
adrenal cortex	UBERON:0001235	87.77	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	87.67	gold quality
adrenal gland	UBERON:0002369	87.44	gold quality
mammary duct	UBERON:0001765	87.13	gold quality
epithelium of mammary gland	UBERON:0003244	87.04	gold quality
right ovary	UBERON:0002118	86.98	gold quality
cardiac muscle of right atrium	UBERON:0003379	86.95	gold quality
right adrenal gland cortex	UBERON:0035827	86.80	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
ADIPOQ	Activation

Upstream regulators (CollecTRI, top): CEBPD

Literature-anchored findings (GeneRIF, showing 17)

• These findings establish a role for TKS4 in Frank-Ter Haar syndrome and embryonic development. (PMID:20137777)
• Tks4 and Tks5 directly bind to NoxA1. The integrity of the N-terminal PRR of NoxA1 is essential for this direct interaction with the Tks proteins. (PMID:20609497)
• The Nox1-dependent generation of reactive oxygen species is dependent on Src phosphorylation of NoxA1 and Tks4. Blockage of phosphorylation of NoxA1 and Tks4 decreases Nox1-dependent ROS generation and blocks SrcYF-induced invadopodia formation. (PMID:20943948)
• SH3PXD2B is a scaffold protein that plays a key role in regulating the actin cytoskeleton via Src and cortactin. (PMID:21886807)
• a new function for Tks4 in the regulation of growth factor-dependent cell migration. (PMID:22829589)
• Misfolded Frank-ter Haar syndrome protein Tks4(R43W) is transported via the microtubule system to the aggresomes. (PMID:26183326)
• Suggest the importance of Tks adaptor proteins in melanoma growth and metastasis in vivo is likely via functional invadopodia formation. (PMID:27802184)
• We report a sibling pair with Frank-ter Haar syndrome (FTHS) caused by a homozygous, novel mutation pLys133Glnfs*13 in the SH3PXD2B gene. (PMID:29100834)
• The interaction of Tks4 with Src may result in the long term stabilization of the kinase in its active conformation, leading to prolonged Src activity following epidermal growth factor stimulation. (PMID:29928795)
• Significance of the Tks4 scaffold protein in bone tissue homeostasis. (PMID:30962481)
• Enhanced endothelial motility and multicellular sprouting is mediated by the scaffold protein TKS4. (PMID:31591456)
• Absence of the Tks4 Scaffold Protein Induces Epithelial-Mesenchymal Transition-Like Changes in Human Colon Cancer Cells. (PMID:31671862)
• Absence of Scaffold Protein Tks4 Disrupts Several Signaling Pathways in Colon Cancer Cells. (PMID:36674824)
• Comprehensive bioinformatics and experimental analysis of SH3PXD2B reveals its carcinogenic effect in gastric carcinoma. (PMID:37211344)
• Studying the Association of TKS4 and CD2AP Scaffold Proteins and Their Implications in the Partial Epithelial-Mesenchymal Transition (EMT) Process. (PMID:37894817)
• Morphological Changes Induced by TKS4 Deficiency Can Be Reversed by EZH2 Inhibition in Colorectal Carcinoma Cells. (PMID:38672463)
• Unveiling epithelial plasticity regulation in lung cancer: Exploring the cross-talk among Tks4 scaffold protein partners. (PMID:38985526)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	sh3pxd2b	ENSDARG00000103251
mus_musculus	Sh3pxd2b	ENSMUSG00000040711
rattus_norvegicus	Sh3pxd2b	ENSRNOG00000004063

Paralogs (3): SH3PXD2A (ENSG00000107957), NCF1 (ENSG00000158517), NOXO1 (ENSG00000196408)

Protein

Protein identifiers

SH3 and PX domain-containing protein 2B — A1X283 (reviewed: A1X283)

Alternative names: Adapter protein HOFI, Factor for adipocyte differentiation 49, Tyrosine kinase substrate with four SH3 domains

All UniProt accessions (4): A1X283, A0A1B0GUF2, G3V144, H0YAU1

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Interacts with ADAM15. Interacts with NOXO1. Interacts (via SH3 domains) with NOXA1; the interaction is direct. Interacts with FASLG.

Subcellular location. Cytoplasm. Cell projection. Podosome.

Tissue specificity. Expressed in fibroblasts.

Post-translational modifications. Phosphorylated in SRC-transformed cells.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The PX domain is required for podosome localization because of its ability to bind phosphatidylinositol 3-phosphate (PtdIns(3)P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) and, to a lesser extent, phosphatidylinositol 4-phosphate (PtdIns(4)P), phosphatidylinositol 5-phosphate (PtdIns(5)P), and phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Binds to the third intramolecular SH3 domain.

Similarity. Belongs to the SH3PXD2 family.

RefSeq proteins (2): NP_001017995, NP_001295104 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR001683	PX_dom	Domain
IPR035477	SH3PXD2B_SH3_1	Domain
IPR035478	SH3PXD2B_SH3_2	Domain
IPR035479	SH3PXD2B_SH3_3	Domain
IPR035480	SH3PXD2B_SH3_4	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR036871	PX_dom_sf	Homologous_superfamily
IPR037961	SH3PXD2_PX	Domain
IPR051228	NADPH_Oxidase/PX-Domain	Family

Pfam: PF00018, PF00787, PF07653

UniProt features (30 total): compositionally biased region 11, modified residue 6, domain 5, sequence conflict 3, sequence variant 2, region of interest 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A1X283-F1	56.95	0.08

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (6): 25, 279, 291, 499, 528, 843

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 358 (showing top): GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_SUPEROXIDE_METABOLIC_PROCESS, PATIL_LIVER_CANCER, GOBP_BONE_DEVELOPMENT, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, GOMF_SH2_DOMAIN_BINDING, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, GOBP_ORGANELLE_ASSEMBLY, GOBP_SUPEROXIDE_ANION_GENERATION, GOBP_EXTRACELLULAR_MATRIX_DISASSEMBLY, GOBP_CONNECTIVE_TISSUE_DEVELOPMENT, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOBP_LOCALIZATION_WITHIN_MEMBRANE, LINDVALL_IMMORTALIZED_BY_TERT_DN, RICKMAN_TUMOR_DIFFERENTIATED_MODERATELY_VS_POORLY_UP

GO Biological Process (12): skeletal system development (GO:0001501), eye development (GO:0001654), superoxide metabolic process (GO:0006801), heart development (GO:0007507), extracellular matrix disassembly (GO:0022617), cell differentiation (GO:0030154), superoxide anion generation (GO:0042554), bone development (GO:0060348), adipose tissue development (GO:0060612), podosome assembly (GO:0071800), protein localization to membrane (GO:0072657), reactive oxygen species metabolic process (GO:0072593)

GO Molecular Function (7): phosphatidylinositol-5-phosphate binding (GO:0010314), superoxide-generating NADPH oxidase activator activity (GO:0016176), phosphatidylinositol-3-phosphate binding (GO:0032266), SH2 domain binding (GO:0042169), phosphatidylinositol-3,5-bisphosphate binding (GO:0080025), protein binding (GO:0005515), phosphatidylinositol binding (GO:0035091)

GO Cellular Component (4): podosome (GO:0002102), cytoplasm (GO:0005737), cell projection (GO:0042995), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
animal organ development	3
phosphatidylinositol phosphate binding	3
anion binding	2
cellular anatomical structure	2
system development	1
sensory organ development	1
visual system development	1
reactive oxygen species metabolic process	1
circulatory system development	1
cellular component disassembly	1
extracellular matrix organization	1
cellular developmental process	1
superoxide metabolic process	1
skeletal system development	1
connective tissue development	1
protein-containing complex assembly	1
plasma membrane bounded cell projection assembly	1
intracellular protein localization	1
localization within membrane	1
metabolic process	1
enzyme activator activity	1
superoxide-generating NADPH oxidase activity	1
protein domain specific binding	1
phosphatidylinositol bisphosphate binding	1
binding	1
actin-based cell projection	1
intracellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

1526 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SH3PXD2B	HCLS1	P14317	940
SH3PXD2B	CTTN	Q14247	938
SH3PXD2B	ADAM15	Q13444	889
SH3PXD2B	NOX1	Q9Y5S8	867
SH3PXD2B	MMP14	P50281	816
SH3PXD2B	SRC	P12931	797
SH3PXD2B	WAS	P42768	762
SH3PXD2B	NOX3	Q9HBY0	747
SH3PXD2B	NOXA1	Q86UR1	746
SH3PXD2B	CFL1	P23528	563
SH3PXD2B	CFL2	Q9Y281	562
SH3PXD2B	WASL	O00401	548
SH3PXD2B	INPPL1	O15357	486
SH3PXD2B	SH3YL1	Q96HL8	481
SH3PXD2B	DNM2	P50570	475

IntAct

49 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
NCK2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.640
ITFG2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
ZNF764	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
GRB2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
NCK1	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
FASLG	SH3PXD2B	psi-mi:“MI:0407”(direct interaction)	0.440
SH3PXD2B	CBX5	psi-mi:“MI:0915”(physical association)	0.400
RASA2	SH3PXD2B	psi-mi:“MI:0915”(physical association)	0.400
SH3PXD2B	SH3PXD2B	psi-mi:“MI:0915”(physical association)	0.400
Cep152	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
LIMK1	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
SORT1	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
PIPSL	C1orf226	psi-mi:“MI:0914”(association)	0.350
DBNL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
BCL9L	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
GPBP1L1	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
BBS7	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350

BioGRID (73): SH3PXD2B (Affinity Capture-MS), SH3PXD2B (Co-fractionation), SH3PXD2B (Co-fractionation), SH3PXD2B (Co-fractionation), SH3PXD2B (Affinity Capture-MS), SH3PXD2B (Synthetic Lethality), SH3PXD2B (Affinity Capture-MS), SH3PXD2B (Affinity Capture-MS), SH3PXD2B (Affinity Capture-MS), SH3PXD2B (Proximity Label-MS), SH3PXD2B (Affinity Capture-MS), SH3PXD2B (Affinity Capture-MS), SH3PXD2B (Affinity Capture-MS), SH3PXD2B (Affinity Capture-RNA), SH3PXD2B (Proximity Label-MS)

ESM2 similar proteins: A1X283, A2AAY5, A5D7F8, A5GFW5, A6ND36, D3ZIE4, D3ZUI5, E2RP94, M0R4F8, O15117, O35601, O54967, O75128, O89032, Q04584, Q06649, Q07912, Q13094, Q13625, Q15942, Q17R10, Q17R13, Q1LYG0, Q32LQ1, Q3TC93, Q3UH68, Q498M5, Q4KM52, Q5DTU0, Q5JV73, Q5NBX1, Q5TCZ1, Q5U2X5, Q62523, Q6IQ23, Q6TXD4, Q80TI1, Q8BI17, Q8BZI0, Q8CG79

Diamond homologs: A1X283, A1ZAY1, A2AAY5, A4RE77, A6NI72, A6SED8, A7EK16, A8MVU1, A8N2Y6, A8PWF6, B0CRJ3, F1M707, O00443, O43586, O77774, O89032, P0CP00, P0CP01, P10569, P14598, P29366, P62484, P97814, Q09014, Q1LYG0, Q2HDI2, Q2KJB5, Q54FG5, Q5I0D6, Q5RAY1, Q5TCX8, Q5TCZ1, Q61194, Q6WKZ7, Q7Z8J6, Q8IVI9, Q8VDG6, Q9NYB9, Q9QX73, Q9Y7Z8

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SRC	“up-regulates activity”	SH3PXD2B	phosphorylation
SH3PXD2B	“up-regulates activity”	NOXA1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 40 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by Rho GTPases	7	7.5×	6e-03
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	7	7.3×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

680 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	8
Uncertain significance	321
Likely benign	180
Benign	85

Top pathogenic / likely-pathogenic (18)

Variant ID	HGVS	Classification
188	NM_001017995.3(SH3PXD2B):c.147dup (p.Asp50Ter)	Pathogenic
189	NM_001017995.3(SH3PXD2B):c.969del (p.Arg324fs)	Pathogenic
191	NM_001017995.3(SH3PXD2B):c.76-2A>C	Pathogenic
2110079	NM_001017995.3(SH3PXD2B):c.330del (p.Tyr111fs)	Pathogenic
217131	NM_001017995.2(SH3PXD2B):c.1188+1773_2733+6592del	Pathogenic
280919	NM_001017995.3(SH3PXD2B):c.846del (p.Leu283fs)	Pathogenic
3246453	NC_000005.9:g.(?171821547)(171821663_?)del	Pathogenic
3257545	NM_001017995.3(SH3PXD2B):c.591_592dup (p.Gln198fs)	Pathogenic
446059	NM_001017995.3(SH3PXD2B):c.250C>T (p.Arg84Ter)	Pathogenic
55933	NM_001017995.3(SH3PXD2B):c.401+1G>A	Pathogenic
1325065	NM_001017995.3(SH3PXD2B):c.567G>A (p.Trp189Ter)	Likely pathogenic
1678826	NM_001017995.3(SH3PXD2B):c.396dup (p.Lys133fs)	Likely pathogenic
190	NM_001017995.3(SH3PXD2B):c.127C>T (p.Arg43Trp)	Likely pathogenic
3012155	NM_001017995.3(SH3PXD2B):c.310-2A>G	Likely pathogenic
3622363	NM_001017995.3(SH3PXD2B):c.668-2A>G	Likely pathogenic
4077509	NM_001017995.3(SH3PXD2B):c.157-1G>A	Likely pathogenic
4085613	NM_001017995.3(SH3PXD2B):c.2128C>T (p.Gln710Ter)	Likely pathogenic
4697218	NM_001017995.3(SH3PXD2B):c.785+1G>A	Likely pathogenic

SpliceAI

2542 predictions. Top by Δscore:

Variant	Effect	Δscore
5:172350361:A:AC	donor_gain	1.0000
5:172350362:C:CC	donor_gain	1.0000
5:172350362:CT:C	donor_gain	1.0000
5:172350362:CTCTG:C	donor_gain	1.0000
5:172353885:TA:T	donor_loss	1.0000
5:172353887:CCTGA:C	donor_loss	1.0000
5:172353895:TCC:T	donor_gain	1.0000
5:172354001:CTCCT:C	acceptor_gain	1.0000
5:172354002:TCCT:T	acceptor_gain	1.0000
5:172354003:CCTC:C	acceptor_gain	1.0000
5:172354004:CT:C	acceptor_gain	1.0000
5:172354005:TCTG:T	acceptor_loss	1.0000
5:172354006:C:CC	acceptor_gain	1.0000
5:172354008:G:C	acceptor_gain	1.0000
5:172362866:CCCC:C	acceptor_gain	1.0000
5:172362867:CCC:C	acceptor_gain	1.0000
5:172362867:CCCC:C	acceptor_gain	1.0000
5:172362868:CC:C	acceptor_gain	1.0000
5:172362868:CCC:C	acceptor_gain	1.0000
5:172362869:CC:C	acceptor_gain	1.0000
5:172382034:A:AC	donor_gain	1.0000
5:172382035:C:CT	donor_gain	1.0000
5:172382035:CT:C	donor_gain	1.0000
5:172394557:CCTTA:C	donor_loss	1.0000
5:172394559:TTACC:T	donor_loss	1.0000
5:172394560:TA:T	donor_loss	1.0000
5:172394562:C:A	donor_loss	1.0000
5:172394635:CTTAC:C	acceptor_gain	1.0000
5:172394636:TTAC:T	acceptor_gain	1.0000
5:172394637:TAC:T	acceptor_gain	1.0000

AlphaMissense

5965 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:172339855:G:T	A417D	1.000
5:172339859:A:G	W416R	1.000
5:172339859:A:T	W416R	1.000
5:172339892:A:G	W405R	1.000
5:172339892:A:T	W405R	1.000
5:172350551:A:G	L275P	1.000
5:172350566:G:T	A270D	1.000
5:172353898:A:G	W259R	1.000
5:172353898:A:T	W259R	1.000
5:172353901:A:G	W258R	1.000
5:172353901:A:T	W258R	1.000
5:172358823:A:G	L206P	1.000
5:172358823:A:T	L206H	1.000
5:172358838:A:T	V201D	1.000
5:172358842:A:G	W200R	1.000
5:172358842:A:T	W200R	1.000
5:172358845:C:G	G199R	1.000
5:172358865:A:T	V192D	1.000
5:172358872:A:G	W190R	1.000
5:172358872:A:T	W190R	1.000
5:172358875:A:G	W189R	1.000
5:172358875:A:T	W189R	1.000
5:172382072:A:G	F122S	1.000
5:172382074:G:C	F121L	1.000
5:172382074:G:T	F121L	1.000
5:172382075:A:G	F121S	1.000
5:172382076:A:G	F121L	1.000
5:172382102:A:T	I112N	1.000
5:172382114:A:G	L108P	1.000
5:172382123:A:G	L105P	1.000

dbSNP variants (sampled 300 via entrez): RS1000049273 (5:172438366 T>C), RS1000104839 (5:172444068 G>A,T), RS1000145360 (5:172348706 T>A), RS1000151797 (5:172346266 T>G), RS1000179261 (5:172338080 C>A), RS1000183903 (5:172332652 C>T), RS1000224518 (5:172397560 G>C), RS1000232715 (5:172332872 G>A), RS1000250012 (5:172379968 T>C), RS1000262960 (5:172349199 A>G), RS1000287126 (5:172356764 C>T), RS1000299164 (5:172394874 A>G), RS1000354901 (5:172451514 C>T), RS1000357182 (5:172385286 A>G), RS1000360267 (5:172411125 T>C)

Disease associations

OMIM: gene MIM:613293 | disease phenotypes: MIM:211170, MIM:249420

GenCC curated gene-disease

Disease	Classification	Inheritance
Frank-Ter Haar syndrome	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Frank-Ter Haar syndrome	Definitive	AR

Mondo (1): Frank-Ter Haar syndrome (MONDO:0009579)

Orphanet (2): Dermato-cardio-skeletal syndrome, Borrone type (Orphanet:1266), Frank-Ter Haar syndrome (Orphanet:137834)

HPO phenotypes

86 total (30 of 86 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000154	Wide mouth
HP:0000187	Broad alveolar ridges
HP:0000212	Gingival overgrowth
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000248	Brachycephaly
HP:0000260	Wide anterior fontanel
HP:0000270	Delayed cranial suture closure
HP:0000280	Coarse facial features
HP:0000293	Full cheeks
HP:0000303	Mandibular prognathia
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000337	Broad forehead
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000369	Low-set ears
HP:0000411	Protruding ear
HP:0000431	Wide nasal bridge
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000485	Megalocornea
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures
HP:0000520	Proptosis
HP:0000557	Buphthalmos
HP:0000684	Delayed eruption of teeth
HP:0000689	Dental malocclusion

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002575_2	Body mass index (change over time)	5.000000e-07
GCST002575_6	Body mass index (change over time)	9.000000e-08
GCST005312_42	Menopause (age at onset)	2.000000e-08
GCST008152_141	Weight	6.000000e-06
GCST010396_186	Gut microbiota (bacterial taxa, hurdle binary method)	3.000000e-06
GCST010796_3060	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-09
GCST010796_3061	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST010796_3062	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-10
GCST90020025_692	Waist-to-hip ratio adjusted for BMI	3.000000e-09
GCST90020027_696	Waist-hip index	7.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0005937	longitudinal BMI measurement
EFO:0004704	age at menopause
EFO:0004338	body weight
EFO:0007874	gut microbiome measurement
EFO:0004327	electrocardiography
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537274	Ter Haar syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

43 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression, increases expression	3
bisphenol A	decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	decreases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	increases expression	1
nonachlor	affects methylation, affects expression	1
sodium arsenate	decreases expression	1
trichostatin A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	decreases methylation	1
epigallocatechin gallate	increases expression, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	increases expression	1
bisphenol AF	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Benztropine	affects cotreatment, decreases expression	1
Caffeine	decreases phosphorylation	1
Calcitriol	increases expression	1
Cannabidiol	affects cotreatment, decreases expression	1
Clozapine	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.