CDIPT

Summary

CDIPT (CDP-diacylglycerol–inositol 3-phosphatidyltransferase, HGNC:1769) is a protein-coding gene on chromosome 16p11.2, encoding CDP-diacylglycerol–inositol 3-phosphatidyltransferase (O14735). Catalyzes the biosynthesis of phosphatidylinositol (PtdIns) as well as PtdIns:inositol exchange reaction. It is a selective cancer dependency (DepMap: 83.0% of cell lines).

Phosphatidylinositol breakdown products are ubiquitous second messengers that function downstream of many G protein-coupled receptors and tyrosine kinases regulating cell growth, calcium metabolism, and protein kinase C activity. Two enzymes, CDP-diacylglycerol synthase and phosphatidylinositol synthase, are involved in the biosynthesis of phosphatidylinositol. Phosphatidylinositol synthase, a member of the CDP-alcohol phosphatidyl transferase class-I family, is an integral membrane protein found on the cytoplasmic side of the endoplasmic reticulum and the Golgi apparatus. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 10423 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 36 total — 5 pathogenic, 1 likely-pathogenic
• GTEx eGene: eQTL in 26 tissues, sQTL in 4 (q < 0.05)
• Cancer dependency (DepMap): dependent in 83.0% of screened cell lines
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.04 (unconstrained)
• MANE Select transcript: NM_006319
• Interaction hub: 1,862 STRING partners (top 9% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1769
Approved symbol	CDIPT
Name	CDP-diacylglycerol–inositol 3-phosphatidyltransferase
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	PIS1, PIS
Ensembl gene	ENSG00000103502
Ensembl biotype	protein_coding
OMIM	605893
Entrez	10423

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 10 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000219789

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 3, TSL 3: 3, TSL 5: 3

ENST00000219789, ENST00000561555, ENST00000562041, ENST00000563415, ENST00000563893, ENST00000564296, ENST00000566113, ENST00000567459, ENST00000569956, ENST00000570016, ENST00000853345, ENST00000934102, ENST00000973445, ENST00001035465, ENST00001135225

RefSeq mRNA: 3 — MANE Select: NM_006319 NM_001286585, NM_001286586, NM_006319

CCDS: CCDS10657, CCDS67002

Canonical transcript exons

ENST00000219789 — 6 exons

Exon	Start	End
ENSE00000681573	29862586	29862720
ENSE00001231826	29862815	29863226
ENSE00001548141	29858357	29859334
ENSE00003549659	29859442	29859523
ENSE00003610655	29861106	29861259
ENSE00003654788	29860581	29860662

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 99.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 44.3064 / max 446.2443, expressed in 1823 samples.

Highest expression (Bgee): parotid gland, endothelial cell, cervix squamous epithelium, Brodmann (1909) area 23, sperm.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CDIPT is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 26 tissues and its splicing (sQTL) in 4 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 30 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Cerebellar Hemisphere	eqtl	1.3e-13	-0.42	16:29825787:C:T
Brain Cerebellum	eqtl	2.5e-12	-0.53	16:29798352:ATTTC:A
Cells Cultured fibroblasts	eqtl	2.1e-07	+0.20	16:29858427:G:C
Brain Frontal Cortex BA9	eqtl	4.2e-06	+0.29	16:29858427:G:C
Adipose Visceral Omentum	eqtl	1.0e-05	-0.23	16:29860409:G:A
Whole Blood	eqtl	1.3e-04	+0.08	16:29863614:T:C
Cells EBV-transformed lymphocytes	eqtl	2.4e-04	-1.26	16:29166740:C:T
Esophagus Mucosa	eqtl	4.3e-04	+0.10	16:29863614:T:C
Adrenal Gland	eqtl	6.0e-04	-0.55	16:28951108:C:T
Spleen	eqtl	1.3e-03	-0.58	16:30095661:C:T
Esophagus Gastroesophageal Junction	eqtl	2.9e-03	-0.62	16:30460482:G:T
Esophagus Muscularis	eqtl	3.4e-03	-0.19	16:30059219:C:T
Skin Sun Exposed Lower leg	eqtl	4.5e-03	-0.33	16:30184593:T:C
Adipose Subcutaneous	eqtl	5.8e-03	+0.18	16:29858427:G:C
Skin Not Sun Exposed Suprapubic	eqtl	6.1e-03	+0.08	16:29871169:C:T
Lung	eqtl	6.9e-03	-0.37	16:30716532:C:G
Breast Mammary Tissue	eqtl	7.7e-03	-0.54	16:29285292:A:T
Liver	eqtl	1.3e-02	-0.52	16:29762362:C:CA
Brain Hypothalamus	eqtl	1.3e-02	+0.19	16:29858427:G:C
Brain Cortex	eqtl	1.4e-02	+0.21	16:29858427:G:C

FANTOM5 promoters

7 alternative TSS:

Promoter ID	TPM avg	Samples expressed
156963	39.6898	1823
156962	1.9483	1288
156959	1.1164	768
156960	0.9363	602
156961	0.5632	359
156958	0.0467	20
156964	0.0057	3

Top tissues by expression

showing 100 of 300 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	99.74	gold quality
endothelial cell	CL:0000115	99.58	gold quality
cervix squamous epithelium	UBERON:0006922	99.41	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.23	gold quality
sperm	CL:0000019	99.07	gold quality
middle temporal gyrus	UBERON:0002771	98.98	gold quality
pancreatic ductal cell	CL:0002079	98.97	gold quality
germinal epithelium of ovary	UBERON:0001304	98.95	gold quality
visceral pleura	UBERON:0002401	98.95	gold quality
parietal pleura	UBERON:0002400	98.81	gold quality
gingival epithelium	UBERON:0001949	98.80	gold quality
cardia of stomach	UBERON:0001162	98.77	gold quality
mammary duct	UBERON:0001765	98.73	gold quality
renal medulla	UBERON:0000362	98.71	gold quality
adult organism	UBERON:0007023	98.69	gold quality
male germ cell	CL:0000015	98.65	gold quality
dorsal root ganglion	UBERON:0000044	98.63	gold quality
gingiva	UBERON:0001828	98.60	gold quality
epithelium of mammary gland	UBERON:0003244	98.59	gold quality
pericardium	UBERON:0002407	98.57	gold quality
pleura	UBERON:0000977	98.50	gold quality
pons	UBERON:0000988	98.49	gold quality
trigeminal ganglion	UBERON:0001675	98.44	gold quality
seminal vesicle	UBERON:0000998	98.38	gold quality
pylorus	UBERON:0001166	98.38	gold quality
urethra	UBERON:0000057	98.37	gold quality
nipple	UBERON:0002030	98.30	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.27	gold quality
choroid plexus epithelium	UBERON:0003911	98.25	gold quality
cerebellar hemisphere	UBERON:0002245	98.19	gold quality
pigmented layer of retina	UBERON:0001782	98.18	gold quality
renal glomerulus	UBERON:0000074	98.17	gold quality
cerebellum	UBERON:0002037	98.17	gold quality
cerebellar cortex	UBERON:0002129	98.16	gold quality
retina	UBERON:0000966	98.15	gold quality
skin of hip	UBERON:0001554	98.11	gold quality
amniotic fluid	UBERON:0000173	98.09	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.09	gold quality
ventral tegmental area	UBERON:0002691	98.03	gold quality
superior vestibular nucleus	UBERON:0007227	98.01	gold quality
synovial joint	UBERON:0002217	97.95	gold quality
mammary gland	UBERON:0001911	97.94	gold quality
eye	UBERON:0000970	97.93	gold quality
thoracic mammary gland	UBERON:0005200	97.93	gold quality
metanephric glomerulus	UBERON:0004736	97.92	gold quality
medulla oblongata	UBERON:0001896	97.91	gold quality
penis	UBERON:0000989	97.89	gold quality
CA1 field of hippocampus	UBERON:0003881	97.88	gold quality
palpebral conjunctiva	UBERON:0001812	97.87	gold quality
mucosa of stomach	UBERON:0001199	97.82	gold quality
superficial temporal artery	UBERON:0001614	97.81	gold quality
lower lobe of lung	UBERON:0008949	97.74	gold quality
inferior olivary complex	UBERON:0002127	97.73	gold quality
saphenous vein	UBERON:0007318	97.73	gold quality
mammalian vulva	UBERON:0000997	97.70	gold quality
thymus	UBERON:0002370	97.68	gold quality
vena cava	UBERON:0004087	97.62	gold quality
inferior vagus X ganglion	UBERON:0005363	97.60	gold quality
nephron tubule	UBERON:0001231	97.55	gold quality
metanephros	UBERON:0000081	97.54	gold quality
right ovary	UBERON:0002118	97.53	gold quality
caput epididymis	UBERON:0004358	97.53	gold quality
hair follicle	UBERON:0002073	97.51	gold quality
tibia	UBERON:0000979	97.50	gold quality
left ovary	UBERON:0002119	97.50	gold quality
upper leg skin	UBERON:0004262	97.49	gold quality
jejunal mucosa	UBERON:0000399	97.42	gold quality
fundus of stomach	UBERON:0001160	97.42	gold quality
substantia nigra pars compacta	UBERON:0001965	97.42	gold quality
corpus epididymis	UBERON:0004359	97.42	gold quality
cauda epididymis	UBERON:0004360	97.42	gold quality
apex of heart	UBERON:0002098	97.40	gold quality
trabecular bone tissue	UBERON:0002483	97.38	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.37	gold quality
lower esophagus	UBERON:0013473	97.35	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.35	gold quality
right adrenal gland cortex	UBERON:0035827	97.35	gold quality
adrenal cortex	UBERON:0001235	97.33	gold quality
occipital lobe	UBERON:0002021	97.33	gold quality
kidney epithelium	UBERON:0004819	97.32	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.32	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.31	gold quality
trachea	UBERON:0003126	97.30	gold quality
right adrenal gland	UBERON:0001233	97.21	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.21	gold quality
coronary artery	UBERON:0001621	97.19	gold quality
left adrenal gland cortex	UBERON:0035825	97.19	gold quality
left adrenal gland	UBERON:0001234	97.18	gold quality
primary visual cortex	UBERON:0002436	97.18	gold quality
right atrium auricular region	UBERON:0006631	97.18	gold quality
descending thoracic aorta	UBERON:0002345	97.15	gold quality
cardiac atrium	UBERON:0002081	97.13	gold quality
myometrium	UBERON:0001296	97.12	gold quality
right coronary artery	UBERON:0001625	97.12	gold quality
left coronary artery	UBERON:0001626	97.09	gold quality
sigmoid colon	UBERON:0001159	97.08	gold quality
epithelial cell of pancreas	CL:0000083	97.06	silver quality
subthalamic nucleus	UBERON:0001906	97.03	gold quality
squamous epithelium	UBERON:0006914	97.03	gold quality
thoracic aorta	UBERON:0001515	97.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.33
E-MTAB-7606	no	1128.06

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Locus coeruleus	tissue	88.4
Frontal cortex	tissue	84.3
Parathyroid gland	tissue	82.6	medium
Caudate putamen	tissue	73.6
Ovary	tissue	71.6	low
Hippocampus	tissue	70.6	medium
Vagina	tissue	69.3	not detected
Heart muscle	tissue	67.2	medium
Pituitary gland	tissue	66.0
Nucleus accumbens	tissue	65.9
Postcentral gyrus	tissue	64.9
Salivary gland	tissue	63.3	low
Pancreas	tissue	59.8	low
Adrenal gland	tissue	56.9	medium
Choroid plexus	tissue	56.1
Adipose tissue	tissue	55.1	medium
Seminal vesicle	tissue	52.3	medium
Pons	tissue	52.2
Substantia nigra	tissue	49.5
Gallbladder	tissue	48.4	low
Hypothalamus	tissue	45.9
Spinal cord	tissue	45.9
Thalamus	tissue	44.6
Skin 1	tissue	44.4	not detected
Fallopian tube	tissue	41.9	medium
Prostate	tissue	41.7	low
Urinary bladder	tissue	41.6	low
Medulla oblongata	tissue	41.1
Tongue	tissue	41.0
Small intestine	tissue	40.9	low
Midbrain	tissue	40.4
Liver	tissue	40.2	medium
Superior colliculi	tissue	40.1
Placenta	tissue	39.8	low
Cervix	tissue	39.7	not detected
Lung	tissue	39.7	low
Endometrium 1	tissue	39.5	low
Thymus	tissue	37.9
Thyroid gland	tissue	37.7	low
Cerebellum	tissue	37.4	medium
Duodenum	tissue	36.6	low
Prefrontal cortex	tissue	36.4
Cerebral cortex	tissue	36.4	medium
Periaqueductal gray	tissue	36.4
Smooth muscle	tissue	36.3	low
Septum	tissue	36.3
Spleen	tissue	35.9	not detected
Stomach 1	tissue	35.0	medium
Hippocampal formation	tissue	34.9
Ventral forebrain	tissue	34.4
Somatosensory cortex	tissue	34.3
Colon	tissue	34.1	low
Lymph node	tissue	33.8	not detected
Esophagus	tissue	33.5	not detected
Kidney	tissue	33.0	medium
Retrosplenial and cingulate cortex	tissue	32.5
Motor cortex	tissue	32.4
Skeletal muscle	tissue	32.0	low
Retina	tissue	31.6
Basal ganglia	tissue	31.5	medium

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Blood vessel (96.8), Nucleus ambiguus (86.3), Cerebellar cortex (86.2), Flocculonodular lobe (84.3), Vermis (83.1).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CDIPT by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

29 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-3925-5P	99.21	67.90	1466
HSA-MIR-5190	99.15	67.76	1234
HSA-MIR-4650-3P	99.01	68.39	1062
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-6529-3P	98.68	66.76	1020
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-6792-5P	98.39	68.16	1330
HSA-MIR-3132	97.96	67.91	711
HSA-MIR-3691-3P	97.90	65.97	791
HSA-MIR-197-5P	97.23	68.10	596
HSA-MIR-3649	96.85	64.10	340
HSA-MIR-3059-3P	96.71	67.08	606
HSA-MIR-550B-3P	95.43	67.73	599
HSA-MIR-5684	93.17	64.85	454
HSA-MIR-4258	90.68	62.19	164

Functional genomics

gnomAD constraint: pLI 0.00394, LOEUF 1.04, missense Z 0.465 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000219789 — one region, missense o/e 0.89. DepMap (CRISPR cell-line fitness): dependent in 83.0% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): PE/CA-PJ15 (-2.283), TC-71 (-2.203), T.T (-2.17), OVCAR-8 (-2.147), PSN1 (-2.108), UM-UC-3 (-2.074), SU-DHL-5 (-2.066), HSC-4 (-2.054), PA-TU-8988T (-2.04), MHH-ES-1 (-1.994), JH-EsoAd1 (-1.965), KP-4 (-1.962), TOV-112D (-1.805), SNU-1105 (-1.746), LN-428 (-1.731).

Literature-anchored findings (GeneRIF, showing 2)

• AAT Deficiency affects at least 120.5 million carriers and deficient subjects worldwide for the two most prevalent deficiency alleles PIZ. (PMID:16312203)
• Increased CDIPT expression was found to be an early event in oral cancer and a target for smokeless tobacco. (PMID:20426864)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdipt	ENSDARG00000070686
mus_musculus	Cdipt	ENSMUSG00000030682
rattus_norvegicus	Cdipt	ENSRNOG00000024144
drosophila_melanogaster	Pis	FBGN0030670
caenorhabditis_elegans		WBGENE00012897

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:105491) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 5 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased lean body mass	1
increased total body fat amount	1
preweaning lethality, complete penetrance	1
decreased circulating lactate dehydrogenase level	1
embryonic lethality prior to organogenesis	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Salmonella enterica subsp. enterica serovar Choleraesuis str. SC-B67	Q57N57	99.5%	Diamond
Arabidopsis thaliana	Q8GUK6	87.6%	Diamond
Wigglesworthia glossinidia endosymbiont of Glossina brevipalpis	Q8D2N9	59.9%	Diamond
Saccharomyces cerevisiae S288C	P06197	52.7%	Diamond
Schizosaccharomyces pombe 972h-	Q10153	51.3%	Diamond
Candida albicans SC5314	Q59RA2	50.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
PRRT2	protein-coding	112476
KIF22	protein-coding	3835
MAZ	protein-coding	4150
PAGR1	protein-coding	79447
MVP	protein-coding	9961
KCTD13-DT	ncRNA	107984836
KCTD13	protein-coding	253980
ASPHD1	protein-coding	253982
SEZ6L2	protein-coding	26470
MVP-DT	ncRNA	112268170

Protein

Protein identifiers

CDP-diacylglycerol–inositol 3-phosphatidyltransferase — O14735 (reviewed: O14735)

Alternative names: Phosphatidylinositol synthase

All UniProt accessions (5): O14735, A8K3L7, B3KY94, H3BTJ7, H3BUR9

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the biosynthesis of phosphatidylinositol (PtdIns) as well as PtdIns:inositol exchange reaction. May thus act to reduce an excessive cellular PtdIns content. The exchange activity is due to the reverse reaction of PtdIns synthase and is dependent on CMP, which is tightly bound to the enzyme.

Subcellular location. Endoplasmic reticulum membrane. Cell membrane.

Tissue specificity. Detected in placenta (at protein level). Widely expressed. Higher expression in adult liver and skeletal muscle, slightly lower levels seen in pancreas, kidney, lung, placenta, brain, heart, leukocyte, colon, small intestine, ovary, testis, prostate, thymus and spleen. In fetus, expressed in kidney, liver, lung and brain.

Activity regulation. Inhibited by PtdIns (product inhibition), phosphatidylinositol phosphate, and nucleoside di- and tri-phosphates.

Cofactor. Catalytic activity is higher with Mg(2+).

Similarity. Belongs to the CDP-alcohol phosphatidyltransferase class-I family.

Isoforms (3)

UniProt ID	Names	Canonical?
O14735-1	1	yes
O14735-2	2
O14735-3	3

RefSeq proteins (3): NP_001273514, NP_001273515, NP_006310* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000462	CDP-OH_P_trans	Family
IPR014387	CDP_diag_ino_3_P_euk	Family
IPR043130	CDP-OH_PTrfase_TM_dom	Homologous_superfamily
IPR048254	CDP_ALCOHOL_P_TRANSF_CS	Conserved_site

Pfam: PF01066

Enzyme classification (BRENDA)

• EC 2.7.8.11 — CDP-diacylglycerol-inositol 3-phosphatidyltransferase (BRENDA: 28 organisms, 71 substrates, 51 inhibitors, 46 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

12 substrates with measured Km, best-characterized 12. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
MYO-INOSITOL	0.015–2.5	23
CDP-DIACYLGLYCEROL	0.0095–0.21	10
2-DEOXY-CDP-DIACYLGLYCEROL	0.029–0.045	2
CDP-DIPALMITIN	0.0193–0.0195	2
CMP	0.022–2.8	2
CDP-1-STEAROYL-2-ARACHIDONOYLGLYCEROL	0.045	1
CDP-1-STEAROYL-2-OLEOYLGLYCEROL	0.03	1
CDP-DIDECANOYL-SN-GLYCEROL	0.06	1
CDP-DIGLYCERIDE	0.17	1
CDP-DIPALMITOYL-SN-GLYCEROL	0.05	1
CDP-DIPALMITOYLGLYCERIDE	1.35	1
CDP-DISTEAROYLGLYCEROL	0.16	1

Catalyzed reactions (Rhea)

• a CDP-1,2-diacyl-sn-glycerol + myo-inositol = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + CMP + H(+) (RHEA:11580)

UniProt features (30 total): binding site 9, topological domain 7, transmembrane region 6, splice variant 4, chain 1, active site 1, sequence variant 1, sequence conflict 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14735-F1	90.02	0.71

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted membrane proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nuclear membrane; nucleoplasm; plasma membrane

Antibody reliability (HPA): IH enhanced · IF approved

Functional residue map

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

Catalytic / active sites (1)

Position	Role
72	proton acceptor

Ligand- & substrate-binding residues (9)

Position	Role
47	Mg(2+)
50	Mg(2+)
51	a CDP-1,2-diacyl-sn-glycerol
55	a CDP-1,2-diacyl-sn-glycerol
61	a CDP-1,2-diacyl-sn-glycerol
68	Mg(2+)
72	Mg(2+)

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-1483226	Synthesis of PI	curated
R-HSA-1483206	Glycerophospholipid biosynthesis	—
R-HSA-1430728	Metabolism	—
R-HSA-556833	Metabolism of lipids	—
R-HSA-1483257	Phospholipid metabolism	—

MSigDB gene sets: 200 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, SCIBETTA_KDM5B_TARGETS_UP, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, BLALOCK_ALZHEIMERS_DISEASE_UP, chr16p11, JAZAG_TGFB1_SIGNALING_VIA_SMAD4_UP, MORF_PPP6C, GOBP_GLYCEROLIPID_BIOSYNTHETIC_PROCESS, MORF_PPP2R4

GO Biological Process (4): phosphatidylinositol biosynthetic process (GO:0006661), CDP-diacylglycerol metabolic process (GO:0046341), lipid metabolic process (GO:0006629), phospholipid biosynthetic process (GO:0008654)

GO Molecular Function (9): CDP-diacylglycerol-inositol 3-phosphatidyltransferase activity (GO:0003881), diacylglycerol binding (GO:0019992), manganese ion binding (GO:0030145), carbohydrate binding (GO:0030246), alcohol binding (GO:0043178), protein binding (GO:0005515), transferase activity (GO:0016740), phosphotransferase activity, for other substituted phosphate groups (GO:0016780), metal ion binding (GO:0046872)

GO Cellular Component (4): endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

4 top-level categories:

Category	Pathways
Glycerophospholipid biosynthesis	1
Phospholipid metabolism	1
Metabolism of lipids	1
Metabolism	1

GO top-level categories

24 GO namespaces:

Category	Terms
binding	2
glycerophospholipid biosynthetic process	1
phosphatidylinositol metabolic process	1
glycerophospholipid metabolic process	1
primary metabolic process	1
phospholipid metabolic process	1
lipid biosynthetic process	1
organophosphate biosynthetic process	1
CDP-alcohol phosphatidyltransferase activity	1
lipid binding	1
transition metal ion binding	1
small molecule binding	1
catalytic activity	1
transferase activity, transferring phosphorus-containing groups	1
cation binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 17 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
phosphatidylinositol biosynthetic process	BP	direct assay
membrane	CC	direct assay
CDP-diacylglycerol-inositol 3-phosphatidyltransferase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,862 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDIPT	TAMM41	Q96BW9	955
CDIPT	ISYNA1	Q9NPH2	915
CDIPT	PIM1	P11309	902
CDIPT	SERPINA1	P01009	825
CDIPT	DYNLL1	P63167	800
CDIPT	ASPHD1	Q5U4P2	731
CDIPT	KCTD13	Q8WZ19	718
CDIPT	SERPINA3	P01011	685
CDIPT	CEPT1	Q9Y6K0	683
CDIPT	CDS1	Q92903	675
CDIPT	SEZ6L2	Q6UXD5	667
CDIPT	HIRIP3	Q9BW71	667
CDIPT	PGS1	Q32NB8	661
CDIPT	PISD	Q9UG56	661
CDIPT	SELENOI	Q9C0D9	646

IntAct

Human interaction partners of CDIPT in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 67 partners by confidence:

Partner	Interaction type	MIscore	Records
AQP2	physical association	0.560	3
AQP6	physical association	0.560	3
ARL13B	physical association	0.560	3
ATP6V0E1	physical association	0.560	3
BSND	physical association	0.560	3
CD79A	physical association	0.560	3
CGRRF1	physical association	0.560	3
CISD2	physical association	0.560	3
CPLX4	physical association	0.560	3
CYB561	physical association	0.560	3
CYB5R3	physical association	0.560	3
DARS2	physical association	0.560	3
EBP	physical association	0.560	3
ERGIC3	physical association	0.560	3
EVI2B	physical association	0.560	3
FAM209A	physical association	0.560	3
FCGR2A	physical association	0.560	3
FFAR2	physical association	0.560	3
FKBP7	physical association	0.560	3
GJB1	physical association	0.560	3
GOLM1	physical association	0.560	3
GPR101	physical association	0.560	3
GPR151	physical association	0.560	3
GPR152	physical association	0.560	3
GPX8	physical association	0.560	3
HSD17B13	physical association	0.560	3
IER3IP1	physical association	0.560	3
IGFBP6	physical association	0.560	3
JAGN1	physical association	0.560	3
KCNK1	physical association	0.560	3

BioGRID (204 interactions; top human partners by supporting records): DSCC1 (Affinity Capture-MS; 2 records), EGFR (Affinity Capture-MS; 2 records), KRAS (Synthetic Lethality; 2 records), SMAP2 (Affinity Capture-MS; 2 records), STAU1 (Proximity Label-MS; 2 records), TTC5 (Affinity Capture-MS; 2 records), YTHDF1 (Affinity Capture-MS; 2 records), AGPAT6 (Affinity Capture-MS), APP (Reconstituted Complex), AQP2 (Two-hybrid), AQP6 (Two-hybrid), ARF6 (Proximity Label-MS), ARL13B (Two-hybrid), ATG9A (Proximity Label-MS), ATP6V0E1 (Two-hybrid)

Disease & clinical

Genetic variants

Variant evidence for CDIPT: 36 ClinVar records (6 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	1
Uncertain significance	22
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (6)

Showing all 6 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
625605	GRCh37/hg19 16p11.2(chr16:29673203-30133233)	Pathogenic	criteria provided, single submitter	1
625610	GRCh37/hg19 16p11.2(chr16:29827174-30198041)	Pathogenic	criteria provided, single submitter	1
997050	GRCh37/hg19 16p11.2(chr16:29652999-30197341)	Pathogenic	criteria provided, single submitter	1
4880504	GRCh38/hg38 16p11.2(chr16:29427005-30215609)x1	Pathogenic	criteria provided, single submitter	1
979440	GRCh37/hg19 16p11.2(chr16:28488319-30178406)x1	Pathogenic	no assertion criteria provided	1
223114	NC_000016.10:g.(?29602174)(30178709_?)dup	Likely pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore CDIPT’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 26 predictions of 262):

Position(s)	Effect	Δscore	Sites
16:29859440–29859441	donor_loss	1.0000	5
16:29859524–29859525	acceptor_loss	1.0000	4
16:29860579–29860580	donor_loss	1.0000	2
16:29860663–29860664	acceptor_loss	1.0000	4
16:29860664	acceptor_gain	1.0000
16:29861104–29861105	donor_loss	1.0000	3
16:29862813	donor_loss	1.0000
16:29859335–29859336	acceptor_loss	0.9900	3
16:29859440	donor_loss	0.9900
16:29859525	acceptor_loss	0.9900	2

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:605893 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): autism spectrum disorder (MONDO:0005258)

Orphanet (1): NON RARE IN EUROPE: Autism (Orphanet:106)

GWAS associations

1 associations:

Study	Trait	p-value
GCST004599_52	Mean platelet volume	2e-9

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067053 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	Kd	0.993	nM	CHEMBL3752910
9.00	ED50	0.993	nM	CHEMBL3752910
7.24	Kd	58.09	nM	CHEMBL5653589
7.24	ED50	58.09	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148041: Binding affinity to human CDIPT incubated for 45 mins by Kinobead based pull down assay	kd	0.0010	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148041: Binding affinity to human CDIPT incubated for 45 mins by Kinobead based pull down assay	kd	0.0581	uM

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects cotreatment	3
Air Pollutants	increases abundance, decreases expression, affects expression	2
Valproic Acid	increases expression, increases methylation	2
Cyclosporine	decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
sodium arsenite	affects binding, increases reaction	1
CGP 52608	affects binding, increases reaction	1
bisphenol B	increases expression	1
MT19c compound	decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
bisphenol AF	increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Clozapine	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Fluorouracil	affects expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Ozone	affects expression, increases abundance	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651083	Binding	Binding affinity to human CDIPT incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00391261	Phase 4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	Phase 4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	Phase 4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	Phase 4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	Phase 4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	Phase 4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	Phase 4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	Phase 4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	Phase 4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	Phase 4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	Phase 4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	Phase 4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	Phase 4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	Phase 4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	Phase 4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	Phase 4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	Phase 4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	Phase 4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	Phase 4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	Phase 4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	Phase 4	RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT07770152	Phase 4	NOT_YET_RECRUITING	Semaglutide in Youth With Autism Spectrum Disorder
NCT01302964	Phase 3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	Phase 3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	Phase 3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	Phase 3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	Phase 3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	Phase 3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	Phase 3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	Phase 3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	Phase 3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	Phase 3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	Phase 3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	Phase 3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	Phase 3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	Phase 3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	Phase 3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	Phase 3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	Phase 3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	Phase 3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	Phase 3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder
NCT06333964	Phase 3	COMPLETED	A Study to Evaluate the Efficacy and Safety of AST-001 in ASD Children
NCT07257939	Phase 3	NOT_YET_RECRUITING	NTI164 in Autism Spectrum Disorder
NCT07655115	Phase 3	RECRUITING	Single Dose Double-blind, Placebo-controlled Cross-over (SDDBPCCO) Shiftability Study, Will be Followed by a 10-week Open-label Study With Arbaclofen (4 Weeks of Titration and Then 6 Weeks of Active/Stable Treatment). The Effects of Arbaclofen on Target EEG and ERG Metrics Will be Associated With th
NCT00251303	Phase 2	COMPLETED	Riluzole to Treat Child and Adolescent Obsessive-Compulsive Disorder With or Without Autism Spectrum Disorders
NCT00614198	Phase 2	COMPLETED	ScanBrit Dietary Intervention in Autism
NCT00619190	Phase 2	COMPLETED	Study of Aripiprazole to Treat Children and Adolescents With Autism
NCT00709202	Phase 2	COMPLETED	Efficacy and Tolerability Study of Betahistine to Ameliorate Antipsychotic Associated Weight Gain
NCT00846547	Phase 2	COMPLETED	Open-Label Study of the Safety and Tolerability of STX209 in Subjects With Autism Spectrum Disorders
NCT01064973	Phase 2	TERMINATED	An Open Label Extension Study of STX209 in Subjects With Autism Spectrum Disorders
NCT01170325	Phase 2	WITHDRAWN	A Study of Divalproex Sodium in Children With ASD and Epileptiform EEG
NCT01205282	Phase 2	COMPLETED	Dose Finding Study of Pioglitazone in Children With Autism Spectrum Disorders (ASD) (PIO)
NCT01248130	Phase 2	TERMINATED	Omega-3 Fatty Acids Monotherapy in Children and Adolescents With Autism Spectrum Disorders
NCT01248728	Phase 2	COMPLETED	Omega-3 Fatty Acids For Treatment Of Young Children With Autism (OMG)
NCT01256060	Phase 2	COMPLETED	Intranasal Oxytocin for the Treatment of Children and Adolescents With ASD (OXY)
NCT01288716	Phase 2	COMPLETED	Study of Arbaclofen for the Treatment of Social Withdrawal in Subjects With Autism Spectrum Disorders
NCT01300923	Phase 2	COMPLETED	Acamprosate in Youth With Fragile X Syndrome
NCT01366859	Phase 2	COMPLETED	Nutritional Intervention in Children With Autism Using Whey Protein (Immunocal): Impact on Core Areas of Behavior
NCT01372449	Phase 2	COMPLETED	A Multi-site Double-blind Placebo-controlled Trial of Memantine Versus Placebo in Children With Autism (MEM)
NCT01395953	Phase 2	WITHDRAWN	Double-blind Trial of Buspirone for the Treatment of Anxiety in Youth With Autism Spectrum Disorders

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CDIPT across ~30M SureChEMBL compounds — explore on Sugi Predict.