DPH1

Summary

DPH1 (diphthamide biosynthesis 1, HGNC:3003) is a protein-coding gene on chromosome 17p13.3, encoding 2-(3-amino-3-carboxypropyl)histidine synthase subunit 1 (Q9BZG8). Catalyzes the first step of diphthamide biosynthesis, a post-translational modification of histidine which occurs in elongation factor 2. It is a selective cancer dependency (DepMap: 26.5% of cell lines).

The protein encoded by this gene is an enzyme involved in the biosynthesis of diphthamide, a modified histidine found only in elongation factor-2 (EEF2). Diphthamide residues in EEF2 are targeted for ADP-ribosylation by diphtheria toxin and Pseudomonas exotoxin A. Defects in this gene have been associated with both ovarian cancer and autosomal recessive intellectual disability with short stature, craniofacial, and ectodermal anomalies.

Source: NCBI Gene 1801 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental delay with short stature, dysmorphic facial features, and sparse hair (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 236 total — 8 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 50
• Cancer dependency (DepMap): dependent in 26.5% of screened cell lines
• MANE Select transcript: NM_001383

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3003
Approved symbol	DPH1
Name	diphthamide biosynthesis 1
Location	17p13.3
Locus type	gene with protein product
Status	Approved
Aliases	OVCA1
Ensembl gene	ENSG00000108963
Ensembl biotype	protein_coding
OMIM	603527
Entrez	1801

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 7 protein_coding, 7 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000263083, ENST00000263084, ENST00000570477, ENST00000570833, ENST00000570867, ENST00000571418, ENST00000571710, ENST00000572214, ENST00000572248, ENST00000572684, ENST00000572819, ENST00000575162, ENST00000575667, ENST00000575998, ENST00000576129, ENST00000576891, ENST00000607788, ENST00000674200

RefSeq mRNA: 4 — MANE Select: NM_001383 NM_001346574, NM_001346575, NM_001346576, NM_001383

CCDS: CCDS42228

Canonical transcript exons

ENST00000263083 — 13 exons

Exon	Start	End
ENSE00002639140	2030153	2030230
ENSE00003461509	2039755	2039823
ENSE00003482881	2033505	2033657
ENSE00003486000	2033779	2033842
ENSE00003543698	2040218	2040374
ENSE00003546244	2041768	2041875
ENSE00003573506	2040505	2040605
ENSE00003585549	2036529	2036686
ENSE00003590098	2035970	2036091
ENSE00003616936	2036835	2036956
ENSE00003622165	2041103	2041181
ENSE00003649301	2041481	2041621
ENSE00003908897	2042605	2043898

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 97.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.2840 / max 225.5113, expressed in 1816 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158797	32.9375	1816
158799	0.2750	52
158798	0.0715	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pituitary gland	UBERON:0000007	97.69	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.36	gold quality
adenohypophysis	UBERON:0002196	97.32	gold quality
cerebellar hemisphere	UBERON:0002245	97.04	gold quality
cerebellum	UBERON:0002037	97.03	gold quality
cerebellar cortex	UBERON:0002129	97.03	gold quality
right uterine tube	UBERON:0001302	96.98	gold quality
body of pancreas	UBERON:0001150	94.50	gold quality
right frontal lobe	UBERON:0002810	94.36	gold quality
left ovary	UBERON:0002119	94.30	gold quality
prostate gland	UBERON:0002367	94.26	gold quality
right ovary	UBERON:0002118	94.24	gold quality
left uterine tube	UBERON:0001303	94.18	gold quality
fundus of stomach	UBERON:0001160	94.15	gold quality
right lobe of thyroid gland	UBERON:0001119	94.12	gold quality
right adrenal gland	UBERON:0001233	94.07	gold quality
right adrenal gland cortex	UBERON:0035827	94.05	gold quality
left lobe of thyroid gland	UBERON:0001120	94.03	gold quality
left adrenal gland cortex	UBERON:0035825	94.01	gold quality
metanephros cortex	UBERON:0010533	93.86	gold quality
body of uterus	UBERON:0009853	93.73	gold quality
thyroid gland	UBERON:0002046	93.72	gold quality
ovary	UBERON:0000992	93.71	gold quality
left adrenal gland	UBERON:0001234	93.69	gold quality
skin of abdomen	UBERON:0001416	93.61	gold quality
body of stomach	UBERON:0001161	93.59	gold quality
skin of leg	UBERON:0001511	93.58	gold quality
zone of skin	UBERON:0000014	93.54	gold quality
gastrocnemius	UBERON:0001388	93.45	gold quality
apex of heart	UBERON:0002098	93.40	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.05

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting DPH1, 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-4481	100.00	66.42	1669
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-1245B-5P	98.88	66.55	576
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-6818-3P	98.56	68.23	1307
HSA-MIR-6804-5P	98.39	65.77	1084
HSA-MIR-6776-3P	98.38	66.34	655
HSA-MIR-224-5P	98.33	70.12	1256
HSA-MIR-197-3P	98.09	69.23	1004
HSA-MIR-6842-3P	98.07	66.33	1325
HSA-MIR-4639-3P	97.54	67.12	787
HSA-MIR-1287-5P	96.80	65.30	743
HSA-MIR-582-3P	96.69	67.38	1019
HSA-MIR-125B-2-3P	96.69	68.38	1210
HSA-MIR-132-5P	96.61	65.79	115
HSA-MIR-4512	95.26	63.08	371
HSA-MIR-6879-3P	93.93	64.00	759

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 26.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 11)

• OVCA1 could inhibit the proliferation of ovarian cancer cells by p16/cyclin D1 pathway, but not by NF-kappaB (PMID:21487939)
• Methylation of the DPH1 promoter causes immunotoxin resistance in acute lymphoblastic leukemia. (PMID:24070652)
• Results identified a second homozygous missense variant in DPH1, seen in four members of a founder population, and associated with autosomal recessive intellectual disability with short stature, craniofacial, and ectodermal anomalies. (PMID:26220823)
• DPH1 functions as an oncogene in CRC and can be negatively modulated by miR-218-5p to promote CRC tumourigenesis. (PMID:29145210)
• We used WES to identify novel compound heterozygous mutations in DPH1 (c.289delG, p.Glu97Lysfs*8 and c.491T>C, p.Leu164Pro) in a patient from a nonconsanguineous family presenting with intellectual disability, a short stature, craniofacial abnormalities, and external genital abnormalities. (PMID:29362492)
• novel homozygous DPH1 mutation causes intellectual disability and unique craniofacial features (PMID:29410513)
• DPH1 syndrome: two novel variants and structural and functional analyses of seven missense variants identified in syndromic patients. (PMID:30877278)
• Identification of the transcription factor Miz1 as an essential regulator of diphthamide biosynthesis using a CRISPR-mediated genome-wide screen. (PMID:33057331)
• An adult Chinese patient with developmental delay with short stature, dysmorphic features, and sparse hair (Loucks-Innes syndrome). (PMID:33704902)
• The functional variant in promoter of OVCA1 was associated with the risk of gastric cancer in the northeast Chinese Han population. (PMID:34990869)
• DPH1 and DPH2 variants that confer susceptibility to diphthamide deficiency syndrome in human cells and yeast models. (PMID:37675463)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dph1	ENSDARG00000057973
mus_musculus	Dph1	ENSMUSG00000078789
rattus_norvegicus	Dph1	ENSRNOG00000071270
drosophila_melanogaster	Dph1	FBGN0036194
caenorhabditis_elegans		WBGENE00007576

Paralogs (1): DPH2 (ENSG00000132768)

Protein

Protein identifiers

2-(3-amino-3-carboxypropyl)histidine synthase subunit 1 — Q9BZG8 (reviewed: Q9BZG8)

Alternative names: Diphthamide biosynthesis protein 1, Diphtheria toxin resistance protein 1, Ovarian cancer-associated gene 1 protein, S-adenosyl-L-methionine:L-histidine 3-amino-3-carboxypropyltransferase 1

All UniProt accessions (8): Q9BZG8, A0A0A0MTR4, I3L1H5, I3L3X9, K7EQQ6, U3KQN3, V9GYC0, V9GYS2

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the first step of diphthamide biosynthesis, a post-translational modification of histidine which occurs in elongation factor 2. DPH1 and DPH2 transfer a 3-amino-3-carboxypropyl (ACP) group from S-adenosyl-L-methionine (SAM) to a histidine residue, the reaction is assisted by a reduction system comprising DPH3 and a NADH-dependent reductase. Acts as a tumor suppressor.

Subunit / interactions. Component of the 2-(3-amino-3-carboxypropyl)histidine synthase complex composed of DPH1, DPH2, DPH3 and a NADH-dependent reductase. Interacts with DPH2. Interacts with RBM8A.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thymus, mammary gland, colon, small intestine, testis and ovary. Reduced expression in primary breast and ovarian tumors.

Disease relevance. Developmental delay with short stature, dysmorphic facial features, and sparse hair 1 (DEDSSH1) [MIM:616901] An autosomal recessive syndrome characterized by intellectual disability, short stature, and craniofacial and ectodermal anomalies including scaphocephaly with or without craniosynostosis, prominent forehead, sparse eyebrows and hair, hypoplastic toenails and, in some cases, dental anomalies. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 [4Fe-4S] cluster per subunit. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine.

Pathway. Protein modification; peptidyl-diphthamide biosynthesis.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to non sense-mediated mRNA decay.

Similarity. Belongs to the DPH1/DPH2 family. DPH1 subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9BZG8-4	4	yes
Q9BZG8-1	1
Q9BZG8-2	2
Q9BZG8-5	5

RefSeq proteins (4): NP_001333503, NP_001333504, NP_001333505, NP_001374* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016435	DPH1/DPH2	Family
IPR042263	DPH1/DPH2_1	Homologous_superfamily
IPR042264	DPH1/DPH2_2	Homologous_superfamily
IPR042265	DPH1/DPH2_3	Homologous_superfamily

Pfam: PF01866

Catalyzed reactions (Rhea), 1 shown:

• L-histidyl-[translation elongation factor 2] + S-adenosyl-L-methionine = 2-[(3S)-amino-3-carboxypropyl]-L-histidyl-[translation elongation factor 2] + S-methyl-5’-thioadenosine + H(+) (RHEA:36783)

UniProt features (24 total): sequence variant 11, splice variant 4, sequence conflict 3, binding site 3, region of interest 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BZG8-F1	87.00	0.81

Functional residue map

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

Ligand- & substrate-binding residues (3): 110; 214; 342

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5358493	Synthesis of diphthamide-EEF2

MSigDB gene sets: 213 (showing top): AP1_01, NKX25_02, FOXO4_01, CAGCTG_AP4_Q5, PATIL_LIVER_CANCER, BLALOCK_ALZHEIMERS_DISEASE_UP, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_DN, NFE2_01, GATGKMRGCG_UNKNOWN, AP4_01, NELSON_RESPONSE_TO_ANDROGEN_DN, PARENT_MTOR_SIGNALING_UP, TGGAAA_NFAT_Q4_01, GOCC_TRANSFERASE_COMPLEX, TAATTA_CHX10_01

GO Biological Process (2): protein histidyl modification to diphthamide (GO:0017183), fibroblast proliferation (GO:0048144)

GO Molecular Function (6): metal ion binding (GO:0046872), 4 iron, 4 sulfur cluster binding (GO:0051539), 2-(3-amino-3-carboxypropyl)histidine synthase activity (GO:0090560), protein binding (GO:0005515), transferase activity (GO:0016740), iron-sulfur cluster binding (GO:0051536)

GO Cellular Component (7): nucleoplasm (GO:0005654), cytosol (GO:0005829), cell junction (GO:0030054), 2-(3-amino-3-carboxypropyl)histidine synthase complex (GO:0120513), nucleus (GO:0005634), cytoplasm (GO:0005737), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
peptidyl-histidine modification	1
cell population proliferation	1
cation binding	1
iron-sulfur cluster binding	1
transferase activity, transferring alkyl or aryl (other than methyl) groups	1
binding	1
catalytic activity	1
metal cluster binding	1
nuclear lumen	1
cytoplasm	1
transferase complex	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular_component	1

Protein interactions and networks

STRING

1432 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DPH1	DPH5	Q9H2P9	980
DPH1	OVCA2	Q8WZ82	932
DPH1	DPH7	Q9BTV6	924
DPH1	EEF2	P13639	918
DPH1	DPH3	Q96FX2	914
DPH1	RBM8A	Q9Y5S9	848
DPH1	DNAJC24	Q6P3W2	843
DPH1	DPH6	Q7L8W6	810
DPH1	DPH2	Q9BQC3	756
DPH1	PDSS2	Q86YH6	590
DPH1	MAGOH	P50606	572
DPH1	MAGOHB	Q96A72	572
DPH1	IPO5	O00410	548
DPH1	SERGEF	Q9UGK8	530
DPH1	ELP5	Q8TE02	515

IntAct

64 interactions, top by confidence:

A	B	Type	Score
NHERF2	PODXL	psi-mi:“MI:0914”(association)	0.770
WIPI2	BNIP3L	psi-mi:“MI:0914”(association)	0.640
STIM2	PRKAB2	psi-mi:“MI:0914”(association)	0.640
DPH1	TFCP2	psi-mi:“MI:0915”(physical association)	0.560
TFCP2	DPH1	psi-mi:“MI:0915”(physical association)	0.560
EFNB2	FAM171A2	psi-mi:“MI:0914”(association)	0.530
SPINT2	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
KPTN	EIF4G3	psi-mi:“MI:0914”(association)	0.530
RAB30	UBB	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
IMPDH1	BCAT2	psi-mi:“MI:0914”(association)	0.530
GFOD1	PER1	psi-mi:“MI:0914”(association)	0.530
HSPA8	ARHGEF10	psi-mi:“MI:2364”(proximity)	0.480
DPH2	DPH1	psi-mi:“MI:0915”(physical association)	0.400
HSPA8	PPP6C	psi-mi:“MI:0914”(association)	0.350
ZNRD2	KRBA1	psi-mi:“MI:0914”(association)	0.350
RGS20	PGP	psi-mi:“MI:0914”(association)	0.350
ARSG	YDJC	psi-mi:“MI:0914”(association)	0.350
IMPDH1	LCMT2	psi-mi:“MI:0914”(association)	0.350
CARD8	HDAC3	psi-mi:“MI:0914”(association)	0.350
P2RX5	NOP56	psi-mi:“MI:0914”(association)	0.350

BioGRID (97): TFCP2 (Two-hybrid), DPH1 (Affinity Capture-RNA), DPH1 (Affinity Capture-RNA), DPH1 (Affinity Capture-MS), DPH1 (Affinity Capture-MS), DPH1 (Affinity Capture-MS), DPH1 (Affinity Capture-MS), DPH1 (Affinity Capture-MS), DPH1 (Affinity Capture-MS), DPH1 (Affinity Capture-MS), DPH1 (Affinity Capture-MS), DPH1 (Affinity Capture-MS), DPH1 (Co-fractionation), EEF2 (Co-fractionation), DPH1 (Affinity Capture-MS)

ESM2 similar proteins: A0A8C2MDK8, A7SLX5, A7YY46, D3ZEY4, D3ZX08, E9QAM5, O59713, O95822, P0C7A1, P48760, P52333, P52824, Q002B5, Q07071, Q14397, Q15477, Q2KI24, Q2M296, Q2NKY8, Q3SYT1, Q3T7C9, Q3U1Y4, Q3URQ7, Q4R380, Q52L34, Q567W6, Q568Y2, Q5I0I8, Q5NCQ5, Q5ZHX9, Q6GPQ5, Q6NZR5, Q6P5E8, Q8BUI3, Q8BX80, Q8C9A2, Q8NFF5, Q8NFI3, Q91X44, Q920F5

Diamond homologs: A0A8C2MDK8, A7SLX5, B0G132, O59713, P0CN18, P0CN19, P40487, P49958, Q3SYT1, Q3T7C9, Q4IQ72, Q4PA25, Q4X0S7, Q54PW5, Q567W6, Q59MG1, Q5AZJ7, Q5NCQ5, Q5ZHX9, Q6BPU5, Q6C0S8, Q6CLC9, Q6DE00, Q6FTG1, Q6GPQ5, Q75AZ9, Q7SC98, Q8SUZ5, Q9BZG8, A4QN59, A7SKJ3, Q10206, Q757B6, Q7S5C0, Q9CR25, O58832, Q5ZKI2, A0A1D8PL26, P0CN20, P0CN21

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 79 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
Dengue Virus Genome Translation and Replication	5	28.8×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	5
Uncertain significance	167
Likely benign	30
Benign	7

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
1188796	NM_001383.6(DPH1):c.914_927del (p.Glu305fs)	Pathogenic
149261	GRCh38/hg38 17p13.3(chr17:2012699-2644858)x1	Pathogenic
2682284	NM_001383.6(DPH1):c.103G>T (p.Glu35Ter)	Pathogenic
3243118	NC_000017.10:g.(?1648982)(2583634_?)del	Pathogenic
3339380	NM_001383.6(DPH1):c.919C>T (p.Arg307Ter)	Pathogenic
817488	NM_001383.6(DPH1):c.607dup (p.Cys203fs)	Pathogenic
997985	NM_001383.6(DPH1):c.476T>C (p.Leu159Pro)	Pathogenic
997988	NM_001383.6(DPH1):c.320A>G (p.Tyr107Cys)	Pathogenic
1012313	NM_001383.6(DPH1):c.382T>C (p.Tyr128His)	Likely pathogenic
1012314	NM_001383.6(DPH1):c.457del (p.Arg153fs)	Likely pathogenic
1324291	NM_001383.6(DPH1):c.652C>T (p.Arg218Ter)	Likely pathogenic
4072476	NM_001383.6(DPH1):c.1007+1G>A	Likely pathogenic
4277948	NM_001383.6(DPH1):c.400+1G>A	Likely pathogenic

SpliceAI

2826 predictions. Top by Δscore:

Variant	Effect	Δscore
17:2033500:TCTAG:T	acceptor_loss	1.0000
17:2033502:TA:T	acceptor_loss	1.0000
17:2033503:A:AG	acceptor_gain	1.0000
17:2033503:AG:A	acceptor_gain	1.0000
17:2033503:AGGTC:A	acceptor_gain	1.0000
17:2033504:G:GA	acceptor_gain	1.0000
17:2033504:GG:G	acceptor_gain	1.0000
17:2033504:GGT:G	acceptor_gain	1.0000
17:2033504:GGTC:G	acceptor_gain	1.0000
17:2033504:GGTCG:G	acceptor_gain	1.0000
17:2033653:GAAGG:G	donor_gain	1.0000
17:2033655:AGG:A	donor_gain	1.0000
17:2033656:GG:G	donor_gain	1.0000
17:2033656:GGG:G	donor_gain	1.0000
17:2033657:G:GT	donor_gain	1.0000
17:2033657:GG:G	donor_loss	1.0000
17:2033658:G:GG	donor_gain	1.0000
17:2033777:A:AG	acceptor_gain	1.0000
17:2033777:AGT:A	acceptor_gain	1.0000
17:2033778:G:GA	acceptor_gain	1.0000
17:2033778:GT:G	acceptor_gain	1.0000
17:2033778:GTG:G	acceptor_gain	1.0000
17:2036086:GCC:G	donor_gain	1.0000
17:2036088:C:CG	donor_gain	1.0000
17:2036090:GA:G	donor_gain	1.0000
17:2036092:G:GG	donor_gain	1.0000
17:2036527:A:AG	acceptor_gain	1.0000
17:2036528:G:GG	acceptor_gain	1.0000
17:2036952:GTTGT:G	donor_gain	1.0000
17:2036955:GT:G	donor_gain	1.0000

AlphaMissense

2850 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:2039774:T:C	F239L	0.999
17:2039776:C:A	F239L	0.999
17:2039776:C:G	F239L	0.999
17:2036657:A:C	S182R	0.998
17:2036659:C:A	S182R	0.998
17:2036659:C:G	S182R	0.998
17:2036669:T:C	F186L	0.998
17:2036671:T:A	F186L	0.998
17:2036671:T:G	F186L	0.998
17:2039777:C:G	H240D	0.998
17:2036019:T:C	C115R	0.997
17:2036082:A:C	S136R	0.997
17:2036084:T:A	S136R	0.997
17:2036084:T:G	S136R	0.997
17:2036573:T:C	F154L	0.997
17:2036575:T:A	F154L	0.997
17:2036575:T:G	F154L	0.997
17:2036013:G:T	G113W	0.996
17:2036014:G:A	G113E	0.996
17:2036077:G:A	G134D	0.996
17:2039775:T:C	F239S	0.996
17:2041119:T:C	C347R	0.996
17:2036020:G:A	C115Y	0.995
17:2036571:T:A	V153D	0.995
17:2036902:G:A	G214E	0.995
17:2036916:T:C	C219R	0.995
17:2036021:C:G	C115W	0.994
17:2036079:C:G	H135D	0.994
17:2039775:T:G	F239C	0.994
17:2039787:C:T	S243F	0.994

dbSNP variants (sampled 300 via entrez): RS1000112259 (17:2042402 C>G,T), RS1000148954 (17:2043466 T>G), RS1000158334 (17:2029275 G>A,C), RS1000201625 (17:2043215 C>G), RS1000261966 (17:2037739 C>CT), RS1000484055 (17:2042483 A>C), RS1000714759 (17:2038262 C>G), RS1001146133 (17:2041581 A>C,G), RS1001168064 (17:2038080 C>T), RS1001555025 (17:2032783 G>A,T), RS1001609157 (17:2032514 T>C,G), RS1001638547 (17:2032073 G>A), RS1001880923 (17:2031455 G>A,C), RS1001888337 (17:2037791 T>C), RS1001904991 (17:2038465 T>G)

Disease associations

OMIM: gene MIM:603527 | disease phenotypes: MIM:616901, MIM:220200

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental delay with short stature, dysmorphic facial features, and sparse hair 1	Strong	Autosomal recessive
craniofacial dysplasia-short stature-ectodermal anomalies-intellectual disability syndrome	Moderate	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
developmental delay with short stature, dysmorphic facial features, and sparse hair	Definitive	AR

Mondo (5): developmental delay with short stature, dysmorphic facial features, and sparse hair (MONDO:0031632), developmental delay with short stature, dysmorphic facial features, and sparse hair 1 (MONDO:0800438), hydrocephalus (MONDO:0001150), Dandy-Walker syndrome (MONDO:0009072), (MONDO:0014824)

Orphanet (2): Craniofacial dysplasia-short stature-ectodermal anomalies-intellectual disability syndrome (Orphanet:459061), Isolated Dandy-Walker malformation (Orphanet:217)

HPO phenotypes

50 total (30 of 50 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000077	Abnormality of the kidney
HP:0000093	Proteinuria
HP:0000175	Cleft palate
HP:0000238	Hydrocephalus
HP:0000243	Trigonocephaly
HP:0000248	Brachycephaly
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000494	Downslanted palpebral fissures
HP:0000653	Sparse eyelashes
HP:0000687	Widely spaced teeth
HP:0000695	Natal tooth
HP:0000739	Anxiety
HP:0000790	Hematuria
HP:0000805	Enuresis
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001274	Agenesis of corpus callosum
HP:0001305	Dandy-Walker malformation
HP:0001320	Cerebellar vermis hypoplasia
HP:0001522	Death in infancy
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001650	Aortic valve stenosis
HP:0001763	Pes planus

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002875_126	Diisocyanate-induced asthma	1.000000e-06
GCST004861_20	Itch intensity from mosquito bite	8.000000e-07
GCST010461_5	Hepatocyte growth factor levels	3.000000e-07
GCST010703_278	Brain morphology (MOSTest)	2.000000e-15

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006995	response to diisocyanate
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D003616	Dandy-Walker Syndrome	C10.228.140.252.300; C10.228.140.602.500; C10.500.205; C16.131.666.205
D006849	Hydrocephalus	C10.228.140.602

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Smoke	decreases expression, affects expression, increases abundance	2
aristolochic acid I	increases expression	1
TAK-243	increases sumoylation	1
sodium arsenite	decreases expression	1
tamibarotene	increases expression	1
abrine	increases expression	1
Sunitinib	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Thiram	decreases expression	1
Tretinoin	increases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1
Vitamin K 3	affects expression	1
Particulate Matter	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9DL	Ubigene HEK293 DPH1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01323764	PHASE4	COMPLETED	ShuntCheck Versus Radionuclide in Evaluating Shunt Function in Symptomatic NPH Patients
NCT01685450	PHASE4	UNKNOWN	NIMIP: Non Invasive Measurement of the Intracranial Pressure
NCT03513757	PHASE4	COMPLETED	Dexmedetomidine and Propofol for Pediatric MRI Sedation
NCT07547826	PHASE4	NOT_YET_RECRUITING	Efficacy and Cost-Effectiveness of Topical Vancomycin Powder in Preventing Pediatric Ventriculoperitoneal Shunt Infections Across Different Etiologies
NCT00196196	PHASE3	COMPLETED	A Precision and Accuracy Study of the Codman Valve Position Verification (VPV) System.
NCT00286104	PHASE3	COMPLETED	Impact of Ventricular Catheter Used With Antimicrobial Agents on Patients With a Ventricular Catheter
NCT01936272	PHASE3	ACTIVE_NOT_RECRUITING	Randomized Controlled Trial of Shunt vs ETV/CPC for PIH in Ugandan Infants
NCT02425761	PHASE3	UNKNOWN	The CSF Shunt Entry Site Trial
NCT02512809	PHASE3	TERMINATED	Isoflurane-induced Neuroinflammation in Children With Hydrocephalus
NCT04177914	PHASE3	RECRUITING	HCRN Endoscopic Versus Shunt Treatment of Hydrocephalus in Infants
NCT00652470	PHASE2	COMPLETED	A Study Comparing Two Treatments for Infants With Hydrocephalus
NCT05001750	PHASE1	RECRUITING	Prophylactic Antibiotics Useful With Antibiotic Impregnated External Ventricular Drains (EVDs)?
NCT01878136	PHASE1/PHASE2	WITHDRAWN	Effect of Intraventricular tPA Following Aneurysmal Subarachnoid Hemorrhage
NCT05476874	PHASE1/PHASE2	UNKNOWN	Improvement of Peritoneal Catheter Placement in VPS With a Splitable Trocar
NCT00001327	Not specified	COMPLETED	Establishing the Physiology of Syringomyelia
NCT00280904	Not specified	COMPLETED	A Registry for Comparing Catheter-Related Infection Rates Among Various Shunt Systems in the Treatment of Hydrocephalus
NCT00651950	Not specified	WITHDRAWN	Bench Study of Transcutaneous Hydrocephalic Shunt Flow Sensor Alignment Accuracy and Repeatability
NCT00652197	Not specified	COMPLETED	Monitoring Patient Cerebro-Spinal Fluid Drainage With an Ultrasonic Flow Sensor
NCT00652249	Not specified	WITHDRAWN	Diagnosing Malfunctioning Hydrocephalic Shunt Valves With a Flow Sensor
NCT00692744	Not specified	COMPLETED	Quality of Life in Elderly After Aneurysmal Subarachnoid Hemorrhage (SAH)
NCT00743457	Not specified	COMPLETED	Study of Ultrasound of the Eye for Children With Suspected Shunt Failure
NCT00875758	Not specified	COMPLETED	Optimizing Treatment of Post-hemorrhagic Ventricular Dilation in Preterm Infants
NCT00886054	Not specified	UNKNOWN	The Prediction of Intracranial Pressure and Clinical Outcome by Transcranial Doppler in Neurocritical Patients
NCT00946127	Not specified	TERMINATED	ETV Versus Shunt Surgery in Normal Pressure Hydrocephalus
NCT01108965	Not specified	COMPLETED	Study of Shunt Flow Sensor Accuracy in Extra-ventricular Drains.
NCT01191307	Not specified	TERMINATED	Assess Specific Kinds of Children Challenges for Neurologic Devices Study
NCT01556178	Not specified	COMPLETED	Blood and Cerebrospinal Fluid for Pediatric Brain Tumor Research
NCT01797627	Not specified	COMPLETED	Ventricular Size Involvement in Neuropsychological Outcomes in Pediatric Hydrocephalus
NCT01799018	Not specified	COMPLETED	Role of Proteomics and Metallomics in Cerebral Vasospasm Following Subarachnoid Hemorrhage
NCT01811589	Not specified	COMPLETED	Guided Application of Ventricular Catheters
NCT01863329	Not specified	TERMINATED	Comparison of Optic Nerve Sheath Diameter on Retrobulbar Ultrasound Before and After Drainage of Cerebrospinal Fluid in Patient With Hydrocephalus
NCT01863381	Not specified	TERMINATED	Comparison of Continuous Non-Invasive and Invasive Intracranial Pressure Measurement
NCT01865149	Not specified	UNKNOWN	Comparison of Optic Nerve Sheath Diameter on Retrobulbar Ultrasonography Before and After Drainage of Cerebrospinal Fluid in Pediatric Patient With Hydrocephalus
NCT01973764	Not specified	TERMINATED	Intraventricular Drain Insertion: Comparison of Ultrasound-guided and Landmark-based Puncture of the Ventricular System
NCT01976559	Not specified	COMPLETED	Comparison of Continuous Noninvasive and Invasive Intracranial Pressure Measurement–Celda Infusion Subprotocol
NCT02067364	Not specified	UNKNOWN	CRT ShuntCheck Fit & Function Study
NCT02230124	Not specified	ACTIVE_NOT_RECRUITING	Magnetic Resonance Elastography in Hydrocephalus
NCT02381977	Not specified	COMPLETED	Prevalence of Acute Critical Neurological Disease in Children: a Global Epidemiological Assessment
NCT02404740	Not specified	COMPLETED	Noninvasive Intracranial Pressure and Hydrocephalus Patients
NCT02408757	Not specified	TERMINATED	Sonographic Monitoring of Weaning of Cerebrospinal Fluid Drainages