EVC

Summary

EVC (EvC ciliary complex subunit 1, HGNC:3497) is a protein-coding gene on chromosome 4p16.2, encoding EvC complex member EVC (P57679). Component of the EvC complex that positively regulates ciliary Hedgehog (Hh) signaling.

This gene encodes a protein containing a leucine zipper and a transmembrane domain. This gene has been implicated in both Ellis-van Creveld syndrome (EvC) and Weyers acrodental dysostosis.

Source: NCBI Gene 2121 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Ellis-van Creveld syndrome (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 2,134 total — 153 pathogenic, 152 likely-pathogenic
• Phenotypes (HPO): 87
• MANE Select transcript: NM_153717

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3497
Approved symbol	EVC
Name	EvC ciliary complex subunit 1
Location	4p16.2
Locus type	gene with protein product
Status	Approved
Aliases	DWF-1, EVC1
Ensembl gene	ENSG00000072840
Ensembl biotype	protein_coding
OMIM	604831
Entrez	2121

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000264956, ENST00000506240, ENST00000509451, ENST00000514919, ENST00000515113, ENST00000861182, ENST00000960562

RefSeq mRNA: 3 — MANE Select: NM_153717 NM_001306090, NM_001306092, NM_153717

CCDS: CCDS3383, CCDS77896

Canonical transcript exons

ENST00000264956 — 21 exons

Exon	Start	End
ENSE00000394493	5748148	5748306
ENSE00000700477	5752836	5753052
ENSE00000700479	5753785	5753933
ENSE00000700481	5756264	5756362
ENSE00000700482	5783552	5783764
ENSE00001008085	5729307	5729390
ENSE00001008086	5733351	5733435
ENSE00001008087	5731425	5731657
ENSE00001008090	5745204	5745341
ENSE00001136868	5810339	5810450
ENSE00001136871	5809518	5809611
ENSE00001136877	5808201	5808327
ENSE00001136880	5804730	5804841
ENSE00001136886	5801950	5802094
ENSE00001193057	5741716	5741814
ENSE00001286155	5719248	5719373
ENSE00001323861	5711201	5711554
ENSE00001492939	5810953	5814305
ENSE00003478395	5793608	5793717
ENSE00003497050	5798586	5798792
ENSE00003533232	5797022	5797232

Expression profiles

Bgee: expression breadth ubiquitous, 163 present calls, max score 95.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.5558 / max 129.7621, expressed in 1468 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46755	7.5179	1434
46756	4.7446	1191
46757	0.2933	158

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	95.69	gold quality
stromal cell of endometrium	CL:0002255	87.64	gold quality
metanephros cortex	UBERON:0010533	86.32	gold quality
gall bladder	UBERON:0002110	84.50	gold quality
left ovary	UBERON:0002119	84.29	gold quality
descending thoracic aorta	UBERON:0002345	83.84	gold quality
thoracic aorta	UBERON:0001515	83.64	gold quality
ascending aorta	UBERON:0001496	83.57	gold quality
right ovary	UBERON:0002118	83.43	gold quality
tibial nerve	UBERON:0001323	82.22	gold quality
right coronary artery	UBERON:0001625	82.21	gold quality
aorta	UBERON:0000947	82.05	gold quality
calcaneal tendon	UBERON:0003701	81.41	gold quality
ventricular zone	UBERON:0003053	81.27	gold quality
popliteal artery	UBERON:0002250	81.09	gold quality
tibial artery	UBERON:0007610	81.08	gold quality
body of uterus	UBERON:0009853	81.01	gold quality
mucosa of stomach	UBERON:0001199	80.64	gold quality
colonic epithelium	UBERON:0000397	80.31	gold quality
ovary	UBERON:0000992	79.90	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	79.56	gold quality
left uterine tube	UBERON:0001303	79.52	gold quality
left coronary artery	UBERON:0001626	79.39	gold quality
lower esophagus muscularis layer	UBERON:0035833	79.35	gold quality
lower esophagus	UBERON:0013473	79.32	gold quality
endocervix	UBERON:0000458	79.16	gold quality
muscle layer of sigmoid colon	UBERON:0035805	78.55	gold quality
coronary artery	UBERON:0001621	78.33	gold quality
adult mammalian kidney	UBERON:0000082	78.29	gold quality
ectocervix	UBERON:0012249	77.85	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.20

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

131 targeting EVC, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-1976	99.74	65.48	1127

Literature-anchored findings (GeneRIF, showing 16)

• CRMP1 and EVC genes are located near WFS1, the Wolfram syndrome type 1 gene. (PMID:15492864)
• In a consanguineous pedigree diagnosed with EvC and borderline intelligence, a 520-kb homozygous deletion comprising EVC, EVC2, C4orf6, and STK32B, caused by recombination between LINE-1 elements, was detected (PMID:18454448)
• EVC mutation is hypomorphic and that such mutations can cause a phenotype of cardiac and limb defects that is less severe than typical Ellis van Creveld syndrome (PMID:18947413)
• EVC and LBN play roles in cardiovascular development and disease. (PMID:19251731)
• We herein report on the first family from Pakistan with a large number of individuals affected by EVC. DNA sequence analysis led to the identification of the fifth missense mutation in the EVC gene (PMID:19744229)
• The expression of a Weyer variant, but not the expression of a truncated protein that mimics an Ellis-van Creveld syndrome mutation, impairs Hedgehog signal transduction in NIH 3T3 cells in keeping with its dominant effect. (PMID:19810119)
• STK32B and EVC yielded consistent evidence from cleft lip, with or without cleft palate, trios in all four populations. (PMID:20087401)
• Molecular analysis of the EVC and EVC2 genes is helpful in genetic counseling in cases with prenatally detected postaxial polydactyly, thoracic narrowness, short limbs and endocardial cushion defects. (PMID:21199751)
• The epigenetically deregulated EVC appears to play an important role for hedgehog activation. (PMID:24996003)
• sequence analysis identified a novel nonsense mutation (p.Trp234*) in exon 8 of the EVC2 gene and 15 bp duplication in exon 14 of the EVC gene in the two families. (PMID:26580685)
• Sequencing of both EVC and EVC2 identified two novel heterozygous splice site mutations c.384+5G>C in intron 3 and c.1465-1G>A in intron 10 in EVC, which were inherited from mother and father, respectively. (PMID:26621368)
• we detected two novel nonsense mutations and a partial deletion of EVC/EVC2 in two Vietnamese families with EvC. Moreover, we found in one family a missense mutation of EFCAB7, a possible modifier gene in EvC and its related disorders. (PMID:26748586)
• Here, we report on two Mexican families with patients diagnosed with Ellis-van Creveld syndrome. In all cases, molecular analysis by Sanger sequencing identified the same homozygous mutation in exon 12 of EVC, c.1678G>T, which leads to a premature stop codon. (PMID:29229899)
• The molecular mechanism underlying the development of ventricular septal defect induced by the EVC c.343C>G mutation may be due to a reduction in the anti-apoptotic and proliferative abilities of cardiomyocytes via downregulation of Hh pathway activity. (PMID:29257216)
• the whole exome sequencing (WES) in this family revealed two homozygous variants in EVC2 (c.30dupC; p.Thr11Hisfs*45) and TMC1 (c.1696-1G>A) genes. In family B, WES revealed novel compound heterozygous variants (p.Ser307Pro, c.2894+3A>G) in the EVC gene. (PMID:29321360)
• An intrafamilial phenotypic variability in Ellis-Van Creveld syndrome due to a novel 27 bps deletion mutation. (PMID:34037314)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Evc	ENSMUSG00000029122
rattus_norvegicus	Evc	ENSRNOG00000007564

Paralogs (1): EVC2 (ENSG00000173040)

Protein

Protein identifiers

EvC complex member EVC — P57679 (reviewed: P57679)

Alternative names: DWF-1, Ellis-van Creveld syndrome protein

All UniProt accessions (2): P57679, E9PCN4

UniProt curated annotations — full annotation on UniProt →

Function. Component of the EvC complex that positively regulates ciliary Hedgehog (Hh) signaling. Involved in endochondral growth and skeletal development.

Subunit / interactions. Component of the EvC complex composed of EFCAB7, IQCE, EVC2 and EVC; built from two subcomplexes, EVC2:EVC and EFCAB7:IQCE. Interacts with EVC2. Interacts with EFCAB7. Interacts with IQCE.

Subcellular location. Cell membrane. Cytoplasm. Cytoskeleton. Cilium basal body. Cell projection. Cilium. Cilium membrane.

Tissue specificity. Found in the developing vertebral bodies, ribs, upper and lower limbs, heart, kidney, lung.

Disease relevance. Ellis-van Creveld syndrome (EVC) [MIM:225500] An autosomal recessive condition characterized by the clinical tetrad of chondrodystrophy, polydactyly, ectodermal dysplasia and cardiac anomalies. Patients manifest short-limb dwarfism, short ribs, postaxial polydactyly, and dysplastic nails and teeth. Congenital heart defects, most commonly an atrioventricular septal defect, are observed in 60% of affected individuals. The disease is caused by variants affecting the gene represented in this entry. Acrofacial dysostosis, Weyers type (WAD) [MIM:193530] An autosomal dominant condition characterized by dysplastic nails, postaxial polydactyly, dental anomalies, short limbs, short stature and normal intelligence. The phenotype is milder than Ellis-van Creveld syndrome. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (3): NP_001293019, NP_001293021, NP_714928* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026501	Limbin/EVC	Family

UniProt features (27 total): sequence variant 14, compositionally biased region 4, region of interest 4, topological domain 2, chain 1, transmembrane region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P57679-F1	74.49	0.41

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5632684	Hedgehog ‘on’ state
R-HSA-5635838	Activation of SMO

MSigDB gene sets: 319 (showing top): GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_GROWTH, GOBP_BONE_GROWTH, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_BONE_DEVELOPMENT, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_ORGAN_GROWTH, chr4p16, GOBP_REGULATION_OF_SMOOTHENED_SIGNALING_PATHWAY, GOBP_SMOOTHENED_SIGNALING_PATHWAY, GOBP_CONNECTIVE_TISSUE_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_SMOOTHENED_SIGNALING_PATHWAY, GOCC_CELL_PROJECTION_MEMBRANE, GOCC_MEMBRANE_PROTEIN_COMPLEX

GO Biological Process (6): skeletal system development (GO:0001501), endochondral bone growth (GO:0003416), smoothened signaling pathway (GO:0007224), muscle organ development (GO:0007517), positive regulation of smoothened signaling pathway (GO:0045880), cartilage development (GO:0051216)

GO Molecular Function (0):

GO Cellular Component (9): cilium (GO:0005929), ciliary basal body (GO:0036064), ciliary membrane (GO:0060170), plasma membrane protein complex (GO:0098797), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by Hedgehog	1
Hedgehog ‘on’ state	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
animal organ development	2
cilium	2
system development	1
bone growth	1
cell surface receptor signaling pathway	1
muscle structure development	1
smoothened signaling pathway	1
regulation of smoothened signaling pathway	1
positive regulation of signal transduction	1
skeletal system development	1
connective tissue development	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
microtubule organizing center	1
cell projection membrane	1
bounding membrane of organelle	1
plasma membrane	1
membrane protein complex	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

750 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EVC	EVC2	Q86UK5	986
EVC	DHCR24	Q15392	877
EVC	SMO	Q99835	835
EVC	DYNC2H1	Q8NCM8	790
EVC	SUFU	Q9UMX1	676
EVC	NSG1	P42857	639
EVC	WDR35	Q9P2L0	571
EVC	CASP6	P55212	549
EVC	WDR19	Q8NEZ3	521
EVC	IFT80	Q9P2H3	519
EVC	RPGRIP1L	Q68CZ1	508
EVC	KIAA0586	Q9BVV6	506
EVC	KIF7	Q2M1P5	504
EVC	TULP3	O75386	501
EVC	CASP7	P55210	498

IntAct

2 interactions, top by confidence:

A	B	Type	Score
UBTF	EVC	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (7): EVC (Affinity Capture-RNA), EVC (Affinity Capture-RNA), EVC (Affinity Capture-RNA), EVC (Affinity Capture-RNA), EVC (Proximity Label-MS), EVC (Proximity Label-MS), EVC (Proximity Label-MS)

ESM2 similar proteins: A1L3H4, A5A777, A6H754, A7YY97, A9ULR1, B2GV52, C7GUN6, D3ZNV2, P05531, P0CAP1, P33716, P57679, P70281, Q03954, Q0IHJ3, Q28HY7, Q32L59, Q3UIJ9, Q4R764, Q4V9P3, Q58CS6, Q5EB94, Q5I0J4, Q5RA87, Q5XIC3, Q5ZK77, Q60547, Q60595, Q61806, Q63520, Q640Z7, Q6AY08, Q6CQ94, Q6NPG7, Q6P205, Q7L3B6, Q80Y56, Q810N9, Q8BXX9, Q8GYM3

Diamond homologs: P57679, P57680

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

2134 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	153
Likely pathogenic	152
Uncertain significance	563
Likely benign	917
Benign	172

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1013604	NM_153717.3(EVC):c.37_38del (p.Arg13fs)	Pathogenic
1068990	NM_153717.3(EVC):c.2561+1dup	Pathogenic
1069685	NC_000004.11:g.(?5798739)(5798969_?)del	Pathogenic
1069686	NC_000004.11:g.(?5809918)(5811348_?)del	Pathogenic
1069687	NC_000004.11:g.(?5754553)(5755670_?)del	Pathogenic
1069725	NM_153717.3(EVC):c.2145_2146insGCCC (p.Gln716fs)	Pathogenic
1069802	NM_153717.3(EVC):c.720dup (p.Lys241Ter)	Pathogenic
1072443	NM_153717.3(EVC):c.1047_1048del (p.Arg349fs)	Pathogenic
1072476	NM_153717.3(EVC):c.1494del (p.Arg498fs)	Pathogenic
1073032	NM_153717.3(EVC):c.1228G>T (p.Glu410Ter)	Pathogenic
1074895	NM_153717.3(EVC):c.1290_1291delinsAA (p.Trp430_Gln431delinsTer)	Pathogenic
1322837	NM_153717.3(EVC):c.414dup (p.Leu139fs)	Pathogenic
1322838	NM_153717.3(EVC):c.1783_1886+40del	Pathogenic
1332830	NM_153717.3(EVC):c.1327C>T (p.Arg443Ter)	Pathogenic
1370178	NM_153717.3(EVC):c.788C>G (p.Ser263Ter)	Pathogenic
1371302	NM_153717.3(EVC):c.338dup (p.Ala114fs)	Pathogenic
1374481	NM_153717.3(EVC):c.673del (p.Asp225fs)	Pathogenic
1379233	NM_153717.3(EVC):c.2698C>T (p.Gln900Ter)	Pathogenic
1383767	NM_153717.3(EVC):c.2488G>T (p.Glu830Ter)	Pathogenic
1385574	NM_153717.3(EVC):c.2705del (p.Phe902fs)	Pathogenic
1390075	NM_153717.3(EVC):c.1324C>T (p.Gln442Ter)	Pathogenic
1393169	NM_153717.3(EVC):c.90del (p.Ala31fs)	Pathogenic
1396608	NM_153717.3(EVC):c.583del (p.Arg194_Val195insTer)	Pathogenic
1430455	NC_000004.11:g.(?5803667)(5806578_?)del	Pathogenic
1443468	NM_153717.3(EVC):c.16del (p.Ala6fs)	Pathogenic
1445523	NM_153717.3(EVC):c.286A>T (p.Lys96Ter)	Pathogenic
1451247	NM_153717.3(EVC):c.478_481del (p.Ser160fs)	Pathogenic
1451565	NM_153717.3(EVC):c.1971del (p.Thr658fs)	Pathogenic
1452022	NC_000004.11:g.(?5565510)(5811251_?)del	Pathogenic
1452861	NM_153717.3(EVC):c.1818_1821del (p.His607fs)	Pathogenic

SpliceAI

3970 predictions. Top by Δscore:

Variant	Effect	Δscore
4:5719225:A:AG	acceptor_gain	1.0000
4:5729455:A:T	donor_gain	1.0000
4:5741707:T:TA	acceptor_gain	1.0000
4:5741715:GAT:G	acceptor_gain	1.0000
4:5741815:G:GG	donor_gain	1.0000
4:5745200:TCA:T	acceptor_loss	1.0000
4:5745201:CAG:C	acceptor_loss	1.0000
4:5745202:A:AG	acceptor_gain	1.0000
4:5745202:AG:A	acceptor_gain	1.0000
4:5745203:G:GA	acceptor_loss	1.0000
4:5745203:G:GG	acceptor_gain	1.0000
4:5745203:GG:G	acceptor_gain	1.0000
4:5745310:A:T	donor_gain	1.0000
4:5745330:C:G	donor_gain	1.0000
4:5745337:A:G	donor_gain	1.0000
4:5745337:ATAAT:A	donor_gain	1.0000
4:5745338:TAAT:T	donor_gain	1.0000
4:5745340:AT:A	donor_gain	1.0000
4:5745341:TGT:T	donor_loss	1.0000
4:5745342:G:GG	donor_gain	1.0000
4:5748145:C:G	acceptor_gain	1.0000
4:5748145:CAGA:C	acceptor_loss	1.0000
4:5748146:A:AG	acceptor_gain	1.0000
4:5748146:AG:A	acceptor_loss	1.0000
4:5748147:G:GG	acceptor_gain	1.0000
4:5748251:A:T	donor_gain	1.0000
4:5752832:GCA:G	acceptor_loss	1.0000
4:5752834:A:AG	acceptor_gain	1.0000
4:5752834:AG:A	acceptor_gain	1.0000
4:5752834:AGGAC:A	acceptor_gain	1.0000

AlphaMissense

6476 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:5729385:T:C	F127L	0.995
4:5729387:C:A	F127L	0.995
4:5729387:C:G	F127L	0.995
4:5729343:T:C	F113L	0.993
4:5729345:C:A	F113L	0.993
4:5729345:C:G	F113L	0.993
4:5731432:C:A	A131D	0.984
4:5729347:C:A	A114D	0.981
4:5729386:T:C	F127S	0.981
4:5731438:G:A	G133D	0.981
4:5729367:T:G	Y121D	0.978
4:5731434:G:C	D132H	0.977
4:5711483:G:C	G35R	0.976
4:5729388:C:G	R128G	0.976
4:5729344:T:C	F113S	0.974
4:5729344:T:G	F113C	0.974
4:5729389:G:C	R128P	0.973
4:5731437:G:C	G133R	0.973
4:5711484:G:A	G35D	0.970
4:5729356:C:A	A117D	0.970
4:5729374:T:A	I123N	0.970
4:5729386:T:G	F127C	0.970
4:5731435:A:T	D132V	0.970
4:5731438:G:T	G133V	0.967
4:5801977:A:C	S778R	0.967
4:5801979:C:A	S778R	0.967
4:5801979:C:G	S778R	0.967
4:5711495:G:C	G39R	0.965
4:5711496:G:A	G39D	0.964
4:5731425:C:T	P129S	0.963

dbSNP variants (sampled 300 via entrez): RS1000005356 (4:5816754 C>T), RS1000026468 (4:5758960 G>C), RS10000314 (4:5709368 G>A,C,T), RS10000316 (4:5772410 C>T), RS1000038270 (4:5765986 T>A), RS1000070816 (4:5765705 A>T), RS1000080385 (4:5785227 C>T), RS1000099524 (4:5816182 C>T), RS10001029 (4:5788433 A>C,G), RS1000110327 (4:5828221 G>T), RS1000132964 (4:5716060 T>C), RS1000148603 (4:5825136 G>T), RS1000167353 (4:5807498 T>C), RS1000179978 (4:5773807 T>G), RS1000192743 (4:5829551 G>A)

Disease associations

OMIM: gene MIM:604831 | disease phenotypes: MIM:193530, MIM:225500, MIM:256100, MIM:263520

GenCC curated gene-disease

Disease	Classification	Inheritance
acrofacial dysostosis, Weyers type	Definitive	Autosomal recessive
Ellis-van Creveld syndrome	Definitive	Autosomal recessive

Mondo (4): acrofacial dysostosis, Weyers type (MONDO:0008673), Ellis-van Creveld syndrome (MONDO:0009162), nephronophthisis (MONDO:0019005), short-rib thoracic dysplasia 6 with or without polydactyly (MONDO:0009894)

Orphanet (3): Ellis Van Creveld syndrome (Orphanet:289), Acrofacial dysostosis, Weyers type (Orphanet:952), Nephronophthisis (Orphanet:655)

HPO phenotypes

87 total (30 of 87 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000008	Abnormal morphology of female internal genitalia
HP:0000028	Cryptorchidism
HP:0000039	Epispadias
HP:0000047	Hypospadias
HP:0000069	Abnormality of the ureter
HP:0000072	Hydroureter
HP:0000077	Abnormality of the kidney
HP:0000164	Abnormality of the dentition
HP:0000190	Abnormal oral frenulum morphology
HP:0000204	Cleft upper lip
HP:0000233	Thin vermilion border
HP:0000395	Prominent antihelix
HP:0000486	Strabismus
HP:0000601	Hypotelorism
HP:0000668	Hypodontia
HP:0000684	Delayed eruption of teeth
HP:0000691	Microdontia
HP:0000695	Natal tooth
HP:0000698	Conical tooth
HP:0000768	Pectus carinatum
HP:0000773	Short ribs
HP:0000774	Narrow chest
HP:0000888	Horizontal ribs
HP:0000924	Abnormality of the skeletal system
HP:0000968	Ectodermal dysplasia
HP:0001156	Brachydactyly
HP:0001161	Hand polydactyly
HP:0001162	Postaxial hand polydactyly

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010002_447	Refractive error	2.000000e-09
GCST90000025_256	Appendicular lean mass	8.000000e-11
GCST90011900_94	Serum alkaline phosphatase levels	7.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004980	appendicular lean mass
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D004613	Ellis-Van Creveld Syndrome	C05.116.099.708.327; C16.131.077.350.398; C16.131.831.350.398; C16.320.850.250.398; C17.800.804.350.398; C17.800.827.250.398
C536695	Weyers acrofacial dysostosis (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression	2
aristolochic acid I	increases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
abrine	increases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	affects methylation	1
Calcitriol	decreases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Formaldehyde	increases expression	1
Phthalic Acids	increases methylation	1
Selenium	increases expression	1
Smoke	decreases expression	1
Testosterone	affects cotreatment, decreases expression	1
Dronabinol	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Valproic Acid	decreases expression	1
Vincristine	increases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02157038	Not specified	COMPLETED	Neuromuscular Mechanisms Underlying Poor Recovery From Whiplash Injuries
NCT01022957	Not specified	COMPLETED	Nephronophthisis : Clinical and Genetic Study
NCT01401998	Not specified	RECRUITING	ARPKD Database Study
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)
NCT05286632	Not specified	COMPLETED	KidneYou - Innovative Digital Therapy
NCT06065852	Not specified	RECRUITING	National Registry of Rare Kidney Diseases
NCT06648044	Not specified	RECRUITING	Research of Therapeutic Targets in the Frame of Nephronophthisis and Renal Associated Ciliopathies