DCHS1

Summary

DCHS1 (dachsous cadherin-related 1, HGNC:13681) is a protein-coding gene on chromosome 11p15.4, encoding Protocadherin-16 (Q96JQ0). Calcium-dependent cell-adhesion protein.

This gene is a member of the cadherin superfamily whose members encode calcium-dependent cell-cell adhesion molecules. The encoded protein has a signal peptide, 27 cadherin repeat domains and a unique cytoplasmic region. This particular cadherin family member is expressed in fibroblasts but not in melanocytes or keratinocytes. The cell-cell adhesion of fibroblasts is thought to be necessary for wound healing.

Source: NCBI Gene 8642 — RefSeq curated summary.

At a glance

• Gene–disease (curated): van Maldergem syndrome 1 (Strong, GenCC) — +4 more curated relationships
• GWAS associations: 6
• Clinical variants (ClinVar): 2,634 total — 30 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 85
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_003737

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13681
Approved symbol	DCHS1
Name	dachsous cadherin-related 1
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	FIB1, KIAA1773, FLJ11790, CDHR6
Ensembl gene	ENSG00000166341
Ensembl biotype	protein_coding
OMIM	603057
Entrez	8642

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 retained_intron

ENST00000299441, ENST00000680123

RefSeq mRNA: 1 — MANE Select: NM_003737 NM_003737

CCDS: CCDS7771

Canonical transcript exons

ENST00000299441 — 21 exons

Exon	Start	End
ENSE00001102272	6633789	6634020
ENSE00001102328	6631616	6631809
ENSE00001102346	6629452	6629577
ENSE00001102351	6626789	6627667
ENSE00001102361	6631053	6631210
ENSE00001102365	6634118	6634306
ENSE00001102369	6628621	6628830
ENSE00001127819	6629672	6629911
ENSE00001127828	6629999	6630863
ENSE00001127854	6632031	6633056
ENSE00001127862	6633412	6633648
ENSE00001127897	6621330	6624390
ENSE00001127905	6639817	6641733
ENSE00001222257	6655563	6655809
ENSE00001323874	6631311	6631407
ENSE00001639827	6625920	6626074
ENSE00001654104	6624730	6624868
ENSE00001681921	6626169	6626380
ENSE00001704381	6625597	6625727
ENSE00001753313	6626552	6626665
ENSE00001758771	6625198	6625481

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 95.84.

FANTOM5 (CAGE): breadth broad, TPM avg 2.9649 / max 79.2866, expressed in 782 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118457	2.5488	723
118456	0.4161	268

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	95.84	gold quality
ganglionic eminence	UBERON:0004023	93.43	gold quality
cortical plate	UBERON:0005343	93.28	gold quality
cartilage tissue	UBERON:0002418	91.42	gold quality
ventricular zone	UBERON:0003053	90.46	gold quality
myometrium	UBERON:0001296	90.05	gold quality
embryo	UBERON:0000922	89.19	gold quality
body of uterus	UBERON:0009853	88.59	gold quality
mucosa of stomach	UBERON:0001199	88.50	gold quality
periodontal ligament	UBERON:0008266	88.03	gold quality
seminal vesicle	UBERON:0000998	87.94	gold quality
saphenous vein	UBERON:0007318	87.35	gold quality
cauda epididymis	UBERON:0004360	86.16	gold quality
layer of synovial tissue	UBERON:0007616	85.87	gold quality
descending thoracic aorta	UBERON:0002345	85.84	gold quality
left uterine tube	UBERON:0001303	85.64	gold quality
synovial joint	UBERON:0002217	85.45	gold quality
stromal cell of endometrium	CL:0002255	84.95	gold quality
muscle layer of sigmoid colon	UBERON:0035805	84.88	gold quality
thoracic aorta	UBERON:0001515	84.59	gold quality
blood vessel layer	UBERON:0004797	84.58	gold quality
ascending aorta	UBERON:0001496	84.44	gold quality
smooth muscle tissue	UBERON:0001135	84.42	gold quality
apex of heart	UBERON:0002098	84.10	gold quality
endocervix	UBERON:0000458	83.94	gold quality
adult organism	UBERON:0007023	83.79	gold quality
mucosa of urinary bladder	UBERON:0001259	83.60	gold quality
urinary bladder	UBERON:0001255	83.33	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	83.03	gold quality
mammary duct	UBERON:0001765	82.98	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.48
E-CURD-112	no	3.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

61 targeting DCHS1, 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-2110	99.96	66.68	1930
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-3191-3P	99.45	63.94	356
HSA-MIR-128-1-5P	99.33	60.46	332
HSA-MIR-128-2-5P	99.33	60.83	311
HSA-MIR-183-5P	99.31	72.27	1164
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4685-5P	99.25	65.99	1563

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 13)

• MMVP2 was found on chromosome 11. (PMID:12707861)
• findings show that mutations in genes encoding the receptor-ligand cadherin pair DCHS1 and FAT4 lead to a recessive syndrome in humans that includes periventricular neuronal heterotopia (PMID:24056717)
• These findings suggest that Fat and Dachsous self-bend due to the loss of Ca(2+)-binding amino acids from specific EC-EC linkers, and can therefore adapt to confined spaces. (PMID:25355906)
• Study shows that when key regulators during mammalian cerebral cortical development are disrupted due to DCHS1-FAT4 mutations, functional cerebral asymmetries are stronger. (PMID:25930014)
• DCHS1 deficiency in mitral valve prolapse patient mitral valve interstitial cells (MVICs), as well as in Dchs1(+/-) mouse MVICs, result in altered migration and cellular patterning, supporting these processes as aetiological underpinnings for the disease (PMID:26258302)
• In sum, we establish Dchs1 as a component of the membrane domain surrounding the ciliary base. This suggests a specific role of Dchs1 in PCP-dependent organization of ciliary function and a possible role in lung disease. (PMID:27074579)
• p.R2330C and p.R2513H were not identified in this cohort. found eight missense variants including six considered deleterious. This includes one novel variant (p.A2464P) and two rare variants (p.R2770Q and p.R2462Q). These variants are predicted to be deleterious with combined annotation-dependent depletion (CADD) scores greater than 25, which are in the same range as p.R2330C (CADD = 28.0) and p.R2513H (CADD = 24.3). (PMID:29224215)
• The infant was diagnosed with van Maldergem syndrome on the basis of the clinical features and this was subsequently confirmed with genetic analysis, which indicated a homozygous mutation (c.7204G>A p. D2402N ) in the DCHS1 gene (PMID:29505454)
• Fat4 and Dchs1 mutants mimic the craniofacial phenotype of the human Van Maldergem syndrome and Dchs1-Fat4 signalling is essential for osteoblast differentiation. (PMID:31358536)
• DCHS1 DNA copy number loss associated with pediatric urinary tract infection risk. (PMID:32295462)
• De novo DCHS1 splicing mutation in a patient with mitral valve prolapse. (PMID:36053189)
• Structure of the planar cell polarity cadherins Fat4 and Dachsous1. (PMID:36797229)
• Mutation in mitral valve prolapse susceptible gene DCHS1 causes familial mitral annular disjunction. (PMID:37399314)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dchs1	ENSMUSG00000036862
rattus_norvegicus	Dchs1	ENSRNOG00000031643

Paralogs (33): CDH1 (ENSG00000039068), CDH10 (ENSG00000040731), CDH3 (ENSG00000062038), CDH19 (ENSG00000071991), CDHR2 (ENSG00000074276), CDH17 (ENSG00000079112), CDH7 (ENSG00000081138), PCDH11Y (ENSG00000099715), CDHR5 (ENSG00000099834), CDH20 (ENSG00000101542), PCDH11X (ENSG00000102290), CDH23 (ENSG00000107736), CDH9 (ENSG00000113100), CDH6 (ENSG00000113361), CDH26 (ENSG00000124215), CDHR3 (ENSG00000128536), CDH15 (ENSG00000129910), CDH24 (ENSG00000139880), CDH11 (ENSG00000140937), CDH13 (ENSG00000140945), CDH18 (ENSG00000145526), CDHR1 (ENSG00000148600), CDH22 (ENSG00000149654), CDH8 (ENSG00000150394), CDH12 (ENSG00000154162), PCDH1 (ENSG00000156453), PCDH7 (ENSG00000169851), CDH2 (ENSG00000170558), CDH4 (ENSG00000179242), CDH5 (ENSG00000179776), PCDH9 (ENSG00000184226), DCHS2 (ENSG00000197410), PCDH20 (ENSG00000280165)

Protein

Protein identifiers

Protocadherin-16 — Q96JQ0 (reviewed: Q96JQ0)

Alternative names: Cadherin-19, Cadherin-25, Fibroblast cadherin-1, Protein dachsous homolog 1

All UniProt accessions (1): Q96JQ0

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-dependent cell-adhesion protein. Mediates functions in neuroprogenitor cell proliferation and differentiation. In the heart, has a critical role for proper morphogenesis of the mitral valve, acting in the regulation of cell migration involved in valve formation.

Subunit / interactions. Heterophilic interaction with FAT4; this interaction affects their respective protein levels.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in fibroblasts but not in melanocytes or keratinocytes.

Disease relevance. Van Maldergem syndrome 1 (VMLDS1) [MIM:601390] An autosomal recessive disorder characterized by intellectual disability, typical craniofacial features, auditory malformations resulting in hearing loss, and skeletal and limb malformations. Some patients have renal hypoplasia. Brain MRI typically shows periventricular nodular heterotopia. The disease is caused by variants affecting the gene represented in this entry. Mitral valve prolapse 2 (MVP2) [MIM:607829] A form of mitral valve prolapse, a valvular heart disease characterized by abnormally elongated and thickened mitral valve leaflets, that typically show myxomatous degeneration with increased leaflet compliance. It is associated with mitral regurgitation. Myxomatous mitral valves have an abnormal layered architecture characterized by loose collagen in fibrosa, expanded spongiosa strongly positive for proteoglycans, and disrupted elastin in atrialis. In classic mitral valve prolapse, leaflets are at least 5 mm thick, whereas in the non-classic form, they are less than 5 mm thick. Severe classic mitral valve prolapse is strongly associated with arrhythmias, endocarditis, heart failure, and need for valve surgery. MVP2 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_003728* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002126	Cadherin-like_dom	Domain
IPR015919	Cadherin-like_sf	Homologous_superfamily
IPR020894	Cadherin_CS	Conserved_site
IPR050971	Cadherin-domain_protein	Family

Pfam: PF00028

UniProt features (99 total): domain 27, strand 24, glycosylation site 14, sequence variant 9, turn 7, helix 5, region of interest 4, compositionally biased region 3, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, modified residue 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8EGW	X-RAY DIFFRACTION	2.3
8EGX	X-RAY DIFFRACTION	3.69

Predicted structure (AlphaFold)

No AlphaFold model available for Q96JQ0 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

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 (1): 3055

Glycosylation sites (14): 217, 256, 402, 584, 1249, 1521, 1718, 1996, 2361, 2428, 2569, 2761, 2792, 2862

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 360 (showing top): AHRARNT_01, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_CELL_MIGRATION_INVOLVED_IN_HEART_DEVELOPMENT, GOBP_HETEROPHILIC_CELL_CELL_ADHESION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_ENDOCARDIAL_CUSHION_DEVELOPMENT, MAZ_Q6, GOBP_NEUROGENESIS, GOBP_NEURAL_TUBE_DEVELOPMENT, TGACCTY_ERR1_Q2, GOBP_HIPPO_SIGNALING, GOBP_KIDNEY_EPITHELIUM_DEVELOPMENT

GO Biological Process (29): branching involved in ureteric bud morphogenesis (GO:0001658), mitral valve formation (GO:0003192), cell migration involved in endocardial cushion formation (GO:0003273), homophilic cell-cell adhesion (GO:0007156), heterophilic cell-cell adhesion (GO:0007157), pattern specification process (GO:0007389), gene expression (GO:0010467), calcium-dependent cell-cell adhesion (GO:0016339), cell migration (GO:0016477), neural tube development (GO:0021915), neurogenesis (GO:0022008), septin cytoskeleton organization (GO:0032185), hippo signaling (GO:0035329), post-anal tail morphogenesis (GO:0036342), ossification involved in bone maturation (GO:0043931), digestive tract development (GO:0048565), condensed mesenchymal cell proliferation (GO:0072137), protein localization to plasma membrane (GO:0072659), cochlea development (GO:0090102), obsolete cell-cell adhesion via plasma-membrane adhesion molecules (GO:0098742), kidney development (GO:0001822), heart morphogenesis (GO:0003007), mitral valve development (GO:0003174), mitral valve morphogenesis (GO:0003183), cell adhesion (GO:0007155), anatomical structure morphogenesis (GO:0009653), tissue morphogenesis (GO:0048729), nephron development (GO:0072006), cell-cell adhesion (GO:0098609)

GO Molecular Function (3): calcium ion binding (GO:0005509), beta-catenin binding (GO:0008013), cadherin binding (GO:0045296)

GO Cellular Component (4): membrane (GO:0016020), catenin complex (GO:0016342), apical part of cell (GO:0045177), plasma membrane (GO:0005886)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell-cell adhesion	3
nervous system development	2
tube development	2
cellular anatomical structure	2
branching morphogenesis of an epithelial tube	1
ureteric bud morphogenesis	1
mitral valve morphogenesis	1
atrioventricular valve formation	1
endocardial cushion formation	1
cell migration involved in heart development	1
multicellular organism development	1
multicellular organismal process	1
macromolecule biosynthetic process	1
cell motility	1
chordate embryonic development	1
epithelium development	1
cell differentiation	1
cytoskeleton organization	1
intracellular signal transduction	1
anatomical structure morphogenesis	1
ossification	1
bone maturation	1
digestive system development	1
mesenchymal cell proliferation	1
protein localization to membrane	1
protein localization to cell periphery	1
inner ear development	1
anatomical structure development	1
metal ion binding	1
protein binding	1
cell adhesion molecule binding	1
extrinsic component of plasma membrane	1
plasma membrane protein complex	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1288 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DCHS1	ARFGEF2	Q9Y6D5	619
DCHS1	SNX8	Q9Y5X2	616
DCHS1	FJX1	Q86VR8	582
DCHS1	CDH17	Q12864	574
DCHS1	FAT4	Q6V0I7	556
DCHS1	ERMARD	Q5T6L9	521
DCHS1	PCDH11X	Q9BZA7	495
DCHS1	FLNA	P21333	454
DCHS1	WDR62	O43379	445
DCHS1	PCDH1	Q08174	423
DCHS1	LMCD1	Q9NZU5	407
DCHS1	PALMD	Q9NP74	391
DCHS1	MOB2	Q70IA6	390
DCHS1	INTS8	Q75QN2	389
DCHS1	CEP63	Q96MT8	382

IntAct

45 interactions, top by confidence:

A	B	Type	Score
ARL4C	RGS12	psi-mi:“MI:0914”(association)	0.640
DKKL1	DENND11	psi-mi:“MI:0914”(association)	0.640
KLK5	DENND11	psi-mi:“MI:0914”(association)	0.640
XAGE1A	THAP12	psi-mi:“MI:0914”(association)	0.530
PCDHGB1	FAM171A2	psi-mi:“MI:0914”(association)	0.530
PPIAL4G	ACTB	psi-mi:“MI:0914”(association)	0.530
CMA1	MANBA	psi-mi:“MI:0914”(association)	0.530
CST6	CTSV	psi-mi:“MI:0914”(association)	0.530
MRPS17	MRPS22	psi-mi:“MI:0914”(association)	0.530
SPSB2	ARHGEF10	psi-mi:“MI:0914”(association)	0.530
SPSB4	ARHGEF10	psi-mi:“MI:0914”(association)	0.530
PCDHGB1	FAM171A2	psi-mi:“MI:0914”(association)	0.350
PPIAL4G	PPIAL4D	psi-mi:“MI:0914”(association)	0.350
DYRK1A	SEC16A	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	POM121C	psi-mi:“MI:0914”(association)	0.350
LLCFC1	POTEF	psi-mi:“MI:0914”(association)	0.350
SPSB4	CCDC85C	psi-mi:“MI:0914”(association)	0.350
PCDHGA7	SDCBP	psi-mi:“MI:0914”(association)	0.350
RYK	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
B4GALT2	NCOR1	psi-mi:“MI:0914”(association)	0.350
PCDHGA6	GOSR1	psi-mi:“MI:0914”(association)	0.350
CDH16	EGFR	psi-mi:“MI:0914”(association)	0.350
DCANP1	IDE	psi-mi:“MI:0914”(association)	0.350
LIX1L	FAT4	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
AURKB	VWA8	psi-mi:“MI:0914”(association)	0.350
C1QA	VWA8	psi-mi:“MI:0914”(association)	0.350
C1QC	VWA8	psi-mi:“MI:0914”(association)	0.350

BioGRID (23): DCHS1 (Affinity Capture-MS), DCHS1 (Affinity Capture-MS), DCHS1 (Affinity Capture-MS), DCHS1 (Affinity Capture-MS), DCHS1 (Affinity Capture-MS), DCHS1 (Affinity Capture-MS), DCHS1 (Affinity Capture-MS), DCHS1 (Affinity Capture-MS), DCHS1 (Affinity Capture-MS), DCHS1 (Affinity Capture-MS), DCHS1 (Affinity Capture-MS), DCHS1 (Affinity Capture-MS), DCHS1 (Affinity Capture-MS), DCHS1 (Affinity Capture-MS), DCHS1 (Affinity Capture-MS)

ESM2 similar proteins: D4ACX8, E9PVD3, O35161, O60500, P33146, P55291, Q2PZL6, Q5DRA2, Q5DRA3, Q5DRA4, Q5DRC3, Q5DRC4, Q5DRC6, Q5DRC7, Q5DRC8, Q5DRC9, Q5DRD1, Q5DRD2, Q5DRD3, Q5DRD6, Q5DRD9, Q5DRF1, Q5SZK8, Q6PFX6, Q6V0I7, Q6V1P9, Q86UP0, Q91XZ2, Q91XZ4, Q96JQ0, Q96MS0, Q96TA0, Q9HCU4, Q9NRJ7, Q9NYQ6, Q9QYP2, Q9R0M0, Q9UN66, Q9UN67, Q9UN70

Diamond homologs: A0A8M9PFP2, B0S5G3, F1R520, O02840, O55111, O88278, O94985, P30944, P33151, P55287, P55288, Q0VCN6, Q14517, Q5DRC8, Q5R9Q9, Q63418, Q6Q0N0, Q6URK6, Q6V1P9, Q86UP0, Q8BNA6, Q8R553, Q8VDA1, Q96JQ0, Q99JH7, Q9BQT9, Q9EPL2, Q9ER65, Q9H4D0, Q9HCU4, Q9NYQ6, Q9R0M0, A7MB46, D3ZE55, D4ACX8, E9PVD3, F8W3X3, O14917, O35161, O55134

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

2634 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	30
Likely pathogenic	8
Uncertain significance	1578
Likely benign	810
Benign	69

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1028154	NM_003737.4(DCHS1):c.5679C>A (p.Tyr1893Ter)	Pathogenic
1072561	NM_003737.4(DCHS1):c.1432C>T (p.Arg478Ter)	Pathogenic
1177398	NM_003737.4(DCHS1):c.2225T>A (p.Leu742Ter)	Pathogenic
1188839	NM_003737.4(DCHS1):c.1964del (p.Phe655fs)	Pathogenic
1455893	NM_003737.4(DCHS1):c.2305C>T (p.Gln769Ter)	Pathogenic
2036143	NM_003737.4(DCHS1):c.5580C>G (p.Tyr1860Ter)	Pathogenic
2124973	NM_003737.4(DCHS1):c.1774_1775del (p.Gln592fs)	Pathogenic
2499546	NM_003737.4(DCHS1):c.163C>T (p.Gln55Ter)	Pathogenic
2693297	NM_003737.4(DCHS1):c.2258del (p.Asn753fs)	Pathogenic
2697356	NM_003737.4(DCHS1):c.5632C>T (p.Gln1878Ter)	Pathogenic
2754963	NM_003737.4(DCHS1):c.4424dup (p.Leu1476fs)	Pathogenic
2767517	NM_003737.4(DCHS1):c.7095del (p.Val2366fs)	Pathogenic
2859078	NM_003737.4(DCHS1):c.4154C>A (p.Ser1385Ter)	Pathogenic
3007006	NM_003737.4(DCHS1):c.5624_5627dup (p.Gln1876fs)	Pathogenic
3652869	NM_003737.4(DCHS1):c.3839del (p.Ile1280fs)	Pathogenic
3658905	NM_003737.4(DCHS1):c.6094C>T (p.Arg2032Ter)	Pathogenic
3663240	NM_003737.4(DCHS1):c.3916C>T (p.Gln1306Ter)	Pathogenic
3664104	NM_003737.4(DCHS1):c.3436C>T (p.Gln1146Ter)	Pathogenic
3666749	NM_003737.4(DCHS1):c.286G>T (p.Glu96Ter)	Pathogenic
3685925	NM_003737.4(DCHS1):c.781dup (p.His261fs)	Pathogenic
4688290	NM_003737.4(DCHS1):c.3782_3825del (p.Ser1261fs)	Pathogenic
4701212	NM_003737.4(DCHS1):c.5580C>A (p.Tyr1860Ter)	Pathogenic
4714939	NM_003737.4(DCHS1):c.6759_6772del (p.Ser2254fs)	Pathogenic
4720375	NM_003737.4(DCHS1):c.61del (p.Leu21fs)	Pathogenic
4726071	NM_003737.4(DCHS1):c.5212C>T (p.Arg1738Ter)	Pathogenic
4729653	NM_003737.4(DCHS1):c.6403G>T (p.Glu2135Ter)	Pathogenic
4760853	NM_003737.4(DCHS1):c.3901C>T (p.Arg1301Ter)	Pathogenic
88997	NM_003737.4(DCHS1):c.2503G>T (p.Gly835Ter)	Pathogenic
88998	NM_003737.4(DCHS1):c.2543del (p.Thr848fs)	Pathogenic
88999	NM_003737.4(DCHS1):c.7109A>T (p.Asn2370Ile)	Pathogenic

SpliceAI

2789 predictions. Top by Δscore:

Variant	Effect	Δscore
11:6624388:TCC:T	acceptor_gain	1.0000
11:6624388:TCCC:T	acceptor_loss	1.0000
11:6624389:CC:C	acceptor_gain	1.0000
11:6624389:CCC:C	acceptor_gain	1.0000
11:6624390:CC:C	acceptor_gain	1.0000
11:6624391:C:CC	acceptor_gain	1.0000
11:6624396:A:AC	acceptor_gain	1.0000
11:6624396:A:C	acceptor_gain	1.0000
11:6624403:C:CT	acceptor_gain	1.0000
11:6624404:G:T	acceptor_gain	1.0000
11:6625591:CCTCA:C	donor_loss	1.0000
11:6625592:CTCA:C	donor_loss	1.0000
11:6625593:TCACC:T	donor_loss	1.0000
11:6625594:CA:C	donor_loss	1.0000
11:6625595:A:T	donor_loss	1.0000
11:6625596:CCTT:C	donor_gain	1.0000
11:6626073:ACC:A	acceptor_loss	1.0000
11:6626075:C:CA	acceptor_loss	1.0000
11:6626163:CCGCA:C	donor_loss	1.0000
11:6626164:CGCAC:C	donor_loss	1.0000
11:6626165:GCAC:G	donor_loss	1.0000
11:6626166:CA:C	donor_loss	1.0000
11:6626167:A:T	donor_loss	1.0000
11:6626377:GCAC:G	acceptor_gain	1.0000
11:6626378:CAC:C	acceptor_gain	1.0000
11:6626378:CACC:C	acceptor_gain	1.0000
11:6626381:C:CC	acceptor_gain	1.0000
11:6626546:TCTTA:T	donor_loss	1.0000
11:6626547:CTTAC:C	donor_loss	1.0000
11:6626548:TTACC:T	donor_loss	1.0000

AlphaMissense

20869 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:6640379:A:C	F412C	1.000
11:6640379:A:G	F412S	1.000
11:6622136:G:C	F3180L	0.999
11:6622136:G:T	F3180L	0.999
11:6622137:A:G	F3180S	0.999
11:6622138:A:G	F3180L	0.999
11:6622187:C:A	W3163C	0.999
11:6622187:C:G	W3163C	0.999
11:6622536:A:G	I3047T	0.999
11:6622545:A:G	I3044T	0.999
11:6624084:A:G	F2531S	0.999
11:6630487:A:C	F1436C	0.999
11:6634128:G:T	A659D	0.999
11:6639881:A:C	F578C	0.999
11:6639887:G:T	P576H	0.999
11:6640025:A:T	I530N	0.999
11:6640217:T:A	N466I	0.999
11:6640278:C:G	D446H	0.999
11:6640283:G:T	A444D	0.999
11:6640289:A:T	V442D	0.999
11:6640439:T:C	D392G	0.999
11:6640451:A:C	I388S	0.999
11:6640451:A:G	I388T	0.999
11:6640451:A:T	I388N	0.999
11:6640457:G:T	A386D	0.999
11:6640458:C:G	A386P	0.999
11:6640460:A:T	V385D	0.999
11:6640535:G:T	P360H	0.999
11:6640679:C:T	G312E	0.999
11:6640680:C:A	G312W	0.999

dbSNP variants (sampled 300 via entrez): RS1000016835 (11:6636748 C>T), RS1000055994 (11:6630623 C>T), RS1000130137 (11:6637872 A>G), RS1000167786 (11:6643013 G>A), RS1000195282 (11:6656941 T>A,C), RS1000340845 (11:6649039 T>C), RS1000532971 (11:6629693 G>C,T), RS1000887004 (11:6649945 A>G), RS1000912886 (11:6655395 C>T), RS1000924980 (11:6625191 T>A,C), RS1000973522 (11:6645673 G>C), RS1001306617 (11:6638326 A>C), RS1001452626 (11:6631735 C>T), RS1001521821 (11:6648214 C>A), RS1001535184 (11:6639569 T>C)

Disease associations

OMIM: gene MIM:603057 | disease phenotypes: MIM:607829, MIM:601390

GenCC curated gene-disease

Disease	Classification	Inheritance
van Maldergem syndrome 1	Strong	Autosomal recessive
mitral valve prolapse, myxomatous 2	Strong	Autosomal dominant
van Maldergem syndrome	Supportive	Autosomal recessive
familial mitral valve prolapse	Supportive	Autosomal dominant
congenital heart disease	Disputed Evidence	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
van Maldergem syndrome	Moderate	AR
congenital heart disease	Disputed	AD

Mondo (8): mitral valve prolapse, myxomatous 2 (MONDO:0011915), congenital heart disease (MONDO:0005453), van Maldergem syndrome 1 (MONDO:0011070), myoepithelial tumor (MONDO:0002380), lymphedema (MONDO:0019297), cardiomyopathy (MONDO:0004994), van Maldergem syndrome (MONDO:0017813), familial mitral valve prolapse (MONDO:0008004)

Orphanet (3): Cerebrofacioarticular syndrome (Orphanet:314679), Rare cardiomyopathy (Orphanet:167848), OBSOLETE: Lymphedema (Orphanet:79383)

HPO phenotypes

85 total (30 of 85 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000047	Hypospadias
HP:0000089	Renal hypoplasia
HP:0000160	Narrow mouth
HP:0000218	High palate
HP:0000239	Large fontanelles
HP:0000252	Microcephaly
HP:0000260	Wide anterior fontanel
HP:0000272	Malar flattening
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000327	Hypoplasia of the maxilla
HP:0000341	Narrow forehead
HP:0000347	Micrognathia
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000413	Atresia of the external auditory canal
HP:0000431	Wide nasal bridge
HP:0000508	Ptosis
HP:0000581	Blepharophimosis
HP:0000689	Dental malocclusion
HP:0000774	Narrow chest
HP:0000894	Short clavicles
HP:0000938	Osteopenia
HP:0000960	Sacral dimple
HP:0001004	Lymphedema
HP:0001159	Syndactyly
HP:0001249	Intellectual disability
HP:0001251	Ataxia

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST009391_2091	Metabolite levels	5.000000e-06
GCST010725_20	Malaria	4.000000e-69
GCST010725_33	Malaria	2.000000e-67
GCST010725_51	Malaria	1.000000e-55
GCST90002384_279	Hemoglobin	2.000000e-09
GCST90002400_631	Plateletcrit	3.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0010373	phosphatidylcholine 32:1 measurement
EFO:0004509	hemoglobin measurement
EFO:0007985	platelet crit

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D009202	Cardiomyopathies	C14.280.238
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D008209	Lymphedema	C15.604.496
D009208	Myoepithelioma	C04.557.435.585
C564326	Mitral Valve Prolapse, Myxomatous 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
Estradiol	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Progesterone	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	increases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects cotreatment	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
perfluorohexanesulfonic acid	decreases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	decreases expression	1
Decitabine	increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Lead	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C1G2	ISFi003-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00115375	PHASE2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	PHASE2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	PHASE2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	PHASE2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	PHASE2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	PHASE2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	PHASE2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	PHASE2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	PHASE2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	PHASE2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	PHASE2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	PHASE2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	PHASE2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE