PLCH1

Summary

PLCH1 (phospholipase C eta 1, HGNC:29185) is a protein-coding gene on chromosome 3q25.31, encoding 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-1 (Q4KWH8). The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by calcium-activated phosphatidylinositol-specific phospholipase C enzymes.

PLCH1 is a member of the PLC-eta family of the phosphoinositide-specific phospholipase C (PLC) superfamily of enzymes that cleave phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) to generate second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) (Hwang et al., 2005 [PubMed 15702972]).

Source: NCBI Gene 23007 — RefSeq curated summary.

At a glance

• Gene–disease (curated): holoprosencephaly 14 (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 267 total — 2 pathogenic
• Phenotypes (HPO): 101
• MANE Select transcript: NM_014996

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29185
Approved symbol	PLCH1
Name	phospholipase C eta 1
Location	3q25.31
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1069, MGC117152, DKFZp434C1372, PLCeta1
Ensembl gene	ENSG00000114805
Ensembl biotype	protein_coding
OMIM	612835
Entrez	23007

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 12 protein_coding, 1 retained_intron

ENST00000334686, ENST00000340059, ENST00000447496, ENST00000460012, ENST00000469040, ENST00000494598, ENST00000897135, ENST00000924317, ENST00000924318, ENST00000924319, ENST00000924320, ENST00000924321, ENST00000968450

RefSeq mRNA: 6 — MANE Select: NM_014996 NM_001130960, NM_001130961, NM_001349250, NM_001349251, NM_001349252, NM_014996

CCDS: CCDS33881, CCDS46939, CCDS46940

Canonical transcript exons

ENST00000460012 — 23 exons

Exon	Start	End
ENSE00000779840	155488028	155488107
ENSE00000779841	155488660	155488806
ENSE00000779842	155490784	155490868
ENSE00000967916	155583472	155583642
ENSE00001076969	155568231	155568324
ENSE00001169674	155549787	155549958
ENSE00001169682	155554076	155554196
ENSE00001169687	155564915	155565118
ENSE00001182591	155485356	155485710
ENSE00001506629	155586065	155586194
ENSE00001506631	155593941	155594184
ENSE00001634529	155514723	155514884
ENSE00001700106	155504555	155504626
ENSE00001734473	155523897	155524004
ENSE00001813708	155704146	155704264
ENSE00001852153	155479881	155483051
ENSE00001948321	155744840	155745071
ENSE00003472361	155500703	155500794
ENSE00003482312	155494141	155494248
ENSE00003482474	155497320	155497417
ENSE00003575073	155492729	155492853
ENSE00003601849	155596232	155596378
ENSE00003650220	155494338	155494517

Expression profiles

Bgee: expression breadth ubiquitous, 200 present calls, max score 87.32.

FANTOM5 (CAGE): breadth broad, TPM avg 3.2583 / max 370.8697, expressed in 497 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45239	2.6957	473
45232	0.3888	97
45231	0.0873	47
45233	0.0548	36
45225	0.0316	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	87.32	gold quality
epithelium of bronchus	UBERON:0002031	86.16	gold quality
ventricular zone	UBERON:0003053	85.24	gold quality
bronchus	UBERON:0002185	84.99	gold quality
choroid plexus epithelium	UBERON:0003911	84.29	gold quality
corpus epididymis	UBERON:0004359	83.84	gold quality
right uterine tube	UBERON:0001302	83.62	gold quality
Brodmann (1909) area 10	UBERON:0013541	83.27	gold quality
pigmented layer of retina	UBERON:0001782	82.58	gold quality
caput epididymis	UBERON:0004358	80.51	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.99	gold quality
endothelial cell	CL:0000115	79.79	gold quality
superior frontal gyrus	UBERON:0002661	78.33	gold quality
Brodmann (1909) area 46	UBERON:0006483	78.21	gold quality
left testis	UBERON:0004533	77.36	gold quality
orbitofrontal cortex	UBERON:0004167	77.21	silver quality
postcentral gyrus	UBERON:0002581	76.76	gold quality
right testis	UBERON:0004534	76.68	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	76.46	gold quality
prefrontal cortex	UBERON:0000451	76.44	gold quality
testis	UBERON:0000473	75.84	gold quality
cingulate cortex	UBERON:0003027	75.71	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	75.69	gold quality
anterior cingulate cortex	UBERON:0009835	75.63	gold quality
cauda epididymis	UBERON:0004360	75.37	gold quality
Brodmann (1909) area 9	UBERON:0013540	74.90	gold quality
parietal lobe	UBERON:0001872	74.67	gold quality
ganglionic eminence	UBERON:0004023	74.60	gold quality
frontal cortex	UBERON:0001870	74.31	gold quality
embryo	UBERON:0000922	74.26	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	690.07
E-ANND-3	yes	12.79
E-GEOD-99795	no	64.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

73 targeting PLCH1, 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-1252-5P	100.00	69.80	2774
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524

Literature-anchored findings (GeneRIF, showing 6)

• molecular cloning of PLC-eta1 and PLC-eta2 (PMID:15583837)
• The identification of a novel PLC isoform in the brains of human and mouse, named PLC-eta, which contains the conserved pleckstrin homology domain, X and Y domains for catalytic activity and the C2 domain. (PMID:15702972)
• The PLCH1 rs181696 single-nucleotide polymorphism was strongly associated with an increased risk of squamous cell carcinoma. (PMID:22658813)
• A molecular model of the PLCeta2 EF-hand domain, constructed based upon the structure of calmodulin, suggested both EF-loops may participate in Ca(2+) -binding. (PMID:24123053)
• High fertilization (56.06%) and pregnancy (41.7%) rates accomplished in this study following ICSI-AOA indicated that expression profiles of PLCzeta, PAWP, and TR-KIT were low in globozoospermic individuals (PMID:27089467)
• Mutations in phospholipase C eta-1 (PLCH1) are associated with holoprosencephaly. (PMID:33820834)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	plch1	ENSDARG00000079253
mus_musculus	Plch1	ENSMUSG00000036834
rattus_norvegicus	Plch1	ENSRNOG00000009955
drosophila_melanogaster	sl	FBGN0003416
drosophila_melanogaster	Plc21C	FBGN0004611
caenorhabditis_elegans		WBGENE00004038
caenorhabditis_elegans		WBGENE00004039
caenorhabditis_elegans		WBGENE00004045

Paralogs (14): PLCB4 (ENSG00000101333), PLCD4 (ENSG00000115556), PLCL1 (ENSG00000115896), PLCG1 (ENSG00000124181), PLCB2 (ENSG00000137841), PLCE1 (ENSG00000138193), PLCZ1 (ENSG00000139151), PLCH2 (ENSG00000149527), PLCB3 (ENSG00000149782), PLCL2 (ENSG00000154822), PLCD3 (ENSG00000161714), PLCB1 (ENSG00000182621), PLCD1 (ENSG00000187091), PLCG2 (ENSG00000197943)

Protein

Protein identifiers

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-1 — Q4KWH8 (reviewed: Q4KWH8)

Alternative names: Phosphoinositide phospholipase C-eta-1, Phospholipase C-eta-1, Phospholipase C-like protein 3

All UniProt accessions (2): Q4KWH8, A0A2U3TZV8

UniProt curated annotations — full annotation on UniProt →

Function. The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by calcium-activated phosphatidylinositol-specific phospholipase C enzymes.

Subcellular location. Cytoplasm. Membrane.

Tissue specificity. Expressed in brain and to a lower extent in lung. In brain, it is found in cerebrum, cerebellum and spinal cord. In embryo expressed in the notochord, developing spinal cord (in a ventral to dorsal gradient), dorsal root ganglia, cerebellum and dermatomyosome.

Disease relevance. Holoprosencephaly 14 (HPE14) [MIM:619895] A form of holoprosencephaly, a structural anomaly of the brain in which the developing forebrain fails to correctly separate into right and left hemispheres. It is a genetically and clinically heterogeneous disorder with a wide spectrum of severity, ranging from alobar holoprosencephaly with severe facial abnormalities, such as cyclopia and proboscis, to mild forms that include lobar or microform holoprosencephaly, without cerebral malformations and with mild craniofacial defects. HPE14 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (4)

UniProt ID	Names	Canonical?
Q4KWH8-1	1, PLC-eta-1	yes
Q4KWH8-2	2
Q4KWH8-3	3, PLC-eta-1a
Q4KWH8-4	4

RefSeq proteins (6): NP_001124432, NP_001124433, NP_001336179, NP_001336180, NP_001336181, NP_055811* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR000909	PLipase_C_PInositol-sp_X_dom	Domain
IPR001192	PI-PLC_fam	Family
IPR001711	PLipase_C_Pinositol-sp_Y	Domain
IPR001849	PH_domain	Domain
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR015359	PLC_EF-hand-like	Domain
IPR017946	PLC-like_Pdiesterase_TIM-brl	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR028392	PLC-eta1_cat	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR046972	PLCeta1_EF	Domain

Pfam: PF00168, PF00387, PF00388, PF09279, PF16457

Enzyme classification (BRENDA):

• EC 3.1.4.11 — phosphoinositide phospholipase C (BRENDA: 69 organisms, 175 substrates, 159 inhibitors, 27 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
1-PHOSPHATIDYL-1D-MYO-INOSITOL 4,5-BISPHOSPHATE	0.006–0.45	8
PHOSPHATIDYLINOSITOL	0.012–100	7
1-PHOSPHATIDYL-1D-MYO-INOSITOL	0.058–18.7	6
PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE	0.031–0.182	3
PHOSPHATIDYLINOSITOL 4-PHOSPHATE	0.031	1

Catalyzed reactions (Rhea), 1 shown:

• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + H2O = 1D-myo-inositol 1,4,5-trisphosphate + a 1,2-diacyl-sn-glycerol + H(+) (RHEA:33179)

UniProt features (45 total): binding site 18, domain 7, splice variant 6, region of interest 5, compositionally biased region 5, active site 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q4KWH8-F1	58.33	0.23

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 (2): 314; 358

Ligand- & substrate-binding residues (18): 155; 157; 159; 166; 315; 344; 346; 393; 442; 444; 627; 654 …

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1855204	Synthesis of IP3 and IP4 in the cytosol

MSigDB gene sets: 344 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOZGIT_ESR1_TARGETS_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_MAINTENANCE_OF_LOCATION, YANG_BREAST_CANCER_ESR1_DN, DELYS_THYROID_CANCER_DN, GOBP_GLYCEROPHOSPHOLIPID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOBP_LIPID_CATABOLIC_PROCESS, GOBP_CALCIUM_ION_TRANSMEMBRANE_TRANSPORT

GO Biological Process (7): lipid catabolic process (GO:0016042), phosphatidylinositol metabolic process (GO:0046488), phosphatidylinositol-mediated signaling (GO:0048015), release of sequestered calcium ion into cytosol (GO:0051209), lipid metabolic process (GO:0006629), signal transduction (GO:0007165), intracellular signal transduction (GO:0035556)

GO Molecular Function (7): phosphatidylinositol-4,5-bisphosphate phospholipase C activity (GO:0004435), calcium ion binding (GO:0005509), obsolete calcium-dependent phospholipase C activity (GO:0050429), C-type glycerophospholipase activity (GO:0004629), phosphoric diester hydrolase activity (GO:0008081), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (4): cytoplasm (GO:0005737), plasma membrane (GO:0005886), cytosol (GO:0005829), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Inositol phosphate metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular anatomical structure	2
lipid metabolic process	1
catabolic process	1
phosphorus metabolic process	1
intracellular signal transduction	1
intercellular transport	1
calcium ion transmembrane import into cytosol	1
primary metabolic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signal transduction	1
C-type glycerophospholipase activity	1
metal ion binding	1
glycerophospholipase activity	1
phosphoric diester hydrolase activity	1
phosphoric ester hydrolase activity	1
catalytic activity	1
cation binding	1
membrane	1
cell periphery	1
cytoplasm	1

Protein interactions and networks

STRING

1064 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLCH1	PLEK2	Q9NYT0	569
PLCH1	PLEK	P08567	525
PLCH1	TIPRL	O75663	517
PLCH1	ISOC1	Q96CN7	456
PLCH1	TMEM210	A6NLX4	447
PLCH1	LIX1	Q8N485	421
PLCH1	ANKS1B	Q7Z6G8	410
PLCH1	RASGEF1C	Q8N431	409
PLCH1	RBPMS	Q93062	403
PLCH1	PHACTR1	Q9C0D0	391
PLCH1	GALNTL6	Q49A17	384
PLCH1	DLGAP1	P78335	383
PLCH1	SDR42E1	Q8WUS8	383
PLCH1	ADAM30	Q9UKF2	369
PLCH1	DLEU7	Q6UYE1	368

IntAct

58 interactions, top by confidence:

A	B	Type	Score
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
EGFR	PLCH1	psi-mi:“MI:0915”(physical association)	0.550
PLCH1	EGFR	psi-mi:“MI:0915”(physical association)	0.550
MTA3	KDM1A	psi-mi:“MI:0914”(association)	0.530
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
N	NOP56	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
HIF1AN	CNOT1	psi-mi:“MI:0914”(association)	0.350
PB2	ESYT2	psi-mi:“MI:0914”(association)	0.350
PB2	IPO5	psi-mi:“MI:0914”(association)	0.350
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
YWHAG	C1orf226	psi-mi:“MI:0914”(association)	0.350
YWHAZ	SPEG	psi-mi:“MI:0914”(association)	0.350
N	RBM47	psi-mi:“MI:0914”(association)	0.350
YWHAB	BRAF	psi-mi:“MI:0914”(association)	0.350
YWHAE	DEPDC5	psi-mi:“MI:0914”(association)	0.350
YWHAG	BRAF	psi-mi:“MI:0914”(association)	0.350
YWHAH	BRAF	psi-mi:“MI:0914”(association)	0.350
YWHAB	FOXO6	psi-mi:“MI:0914”(association)	0.350
YWHAG	FOXO6	psi-mi:“MI:0914”(association)	0.350

BioGRID (100): PLCH1 (Affinity Capture-MS), PLCH1 (Affinity Capture-MS), PLCH1 (Affinity Capture-MS), PLCH1 (Affinity Capture-MS), PLCH1 (Affinity Capture-MS), PLCH1 (Affinity Capture-MS), PLCH1 (Affinity Capture-MS), PLCH1 (Affinity Capture-MS), PLCH1 (Affinity Capture-MS), PLCH1 (Proximity Label-MS), PLCH1 (Proximity Label-MS), PLCH1 (Affinity Capture-MS), PLCH1 (Proximity Label-MS), PLCH1 (Affinity Capture-MS), PLCH1 (Proximity Label-MS)

ESM2 similar proteins: A0A0G2K344, D3ZGS3, F1M386, F1MSG6, F1PBJ0, G5EF51, O00329, O02697, O35242, O35904, O70481, O88763, O94830, P32871, P42336, P42337, P42338, P42339, P42347, P42348, P48736, P50520, P54676, P70600, Q01968, Q14289, Q14BI7, Q16JS8, Q3MHU3, Q3UYK3, Q4KWH5, Q4KWH8, Q5D891, Q5ZI89, Q6AZN6, Q6GQ76, Q6NVF0, Q6PF93, Q7Z392, Q80Y98

Diamond homologs: A2AP18, A3KGF7, A5D6R3, G5EBH0, G5EFI8, O75038, O89040, P10687, P10688, P10894, P10895, P21671, P25455, P51178, P51432, Q00722, Q01970, Q07722, Q15111, Q15147, Q1RML2, Q2VRL0, Q32NH8, Q3USB7, Q4KWH5, Q4KWH8, Q4R6L3, Q5FX52, Q5RET0, Q62688, Q62711, Q6NMA7, Q7YRU3, Q86YW0, Q8K2J0, Q8K394, Q8K3R3, Q8K4D7, Q8K4S1, Q8L706

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 54 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
Activation of BAD and translocation to mitochondria	7	140.2×	3e-12
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	123.8×	5e-12
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	123.8×	5e-12
Activation of BH3-only proteins	7	91.5×	4e-11
RHO GTPases activate PKNs	8	66.8×	2e-11
Intrinsic Pathway for Apoptosis	7	53.9×	2e-09
FOXO-mediated transcription	5	44.2×	2e-06
Negative regulation of MAPK pathway	5	34.9×	5e-06

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	40.7×	4e-05
intracellular protein localization	7	16.3×	4e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	215
Likely benign	15
Benign	4

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1687099	NM_014996.4(PLCH1):c.2101C>T (p.Arg701Ter)	Pathogenic
1687100	NM_014996.4(PLCH1):c.3211del (p.Cys1071fs)	Pathogenic

SpliceAI

5774 predictions. Top by Δscore:

Variant	Effect	Δscore
3:155485706:CTGTT:C	acceptor_gain	1.0000
3:155485707:TGTT:T	acceptor_gain	1.0000
3:155485710:TC:T	acceptor_loss	1.0000
3:155485711:C:CC	acceptor_gain	1.0000
3:155485712:T:A	acceptor_loss	1.0000
3:155488809:C:CT	acceptor_gain	1.0000
3:155488816:A:C	acceptor_gain	1.0000
3:155490778:TCTTA:T	donor_loss	1.0000
3:155490779:CTTA:C	donor_loss	1.0000
3:155490780:TTACC:T	donor_loss	1.0000
3:155490781:TACC:T	donor_loss	1.0000
3:155490782:A:AC	donor_gain	1.0000
3:155490783:C:CC	donor_gain	1.0000
3:155490865:TGAT:T	acceptor_gain	1.0000
3:155490869:C:CC	acceptor_gain	1.0000
3:155492724:CTTA:C	donor_loss	1.0000
3:155492725:TTAC:T	donor_loss	1.0000
3:155492726:TACC:T	donor_loss	1.0000
3:155492727:A:AC	donor_gain	1.0000
3:155492727:A:T	donor_loss	1.0000
3:155492727:AC:A	donor_gain	1.0000
3:155492727:ACCT:A	donor_gain	1.0000
3:155492728:C:CA	donor_gain	1.0000
3:155492728:CC:C	donor_gain	1.0000
3:155492728:CCT:C	donor_gain	1.0000
3:155492728:CCTC:C	donor_gain	1.0000
3:155492728:CCTCG:C	donor_gain	1.0000
3:155492850:GTAC:G	acceptor_gain	1.0000
3:155492851:TAC:T	acceptor_gain	1.0000
3:155492852:ACCTA:A	acceptor_loss	1.0000

AlphaMissense

11171 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:155488792:A:G	W791R	1.000
3:155488792:A:T	W791R	1.000
3:155490852:A:T	V763D	1.000
3:155492780:A:C	S740R	1.000
3:155492780:A:T	S740R	1.000
3:155492782:T:G	S740R	1.000
3:155583611:A:C	L199W	1.000
3:155583611:A:G	L199S	1.000
3:155583639:C:G	A190P	1.000
3:155586120:A:G	L170P	1.000
3:155586144:A:G	L162P	1.000
3:155593998:A:G	L126P	1.000
3:155594007:A:G	L123P	1.000
3:155594020:A:G	W119R	1.000
3:155594020:A:T	W119R	1.000
3:155594052:A:G	L108P	1.000
3:155596265:A:G	W53R	1.000
3:155596265:A:T	W53R	1.000
3:155481295:T:A	R1585S	0.999
3:155481295:T:G	R1585S	0.999
3:155481304:A:C	S1582R	0.999
3:155481304:A:T	S1582R	0.999
3:155481306:T:G	S1582R	0.999
3:155481557:A:G	L1498S	0.999
3:155488095:A:T	V839D	0.999
3:155488101:C:G	R837P	0.999
3:155488725:T:A	D813V	0.999
3:155488725:T:G	D813A	0.999
3:155488737:A:G	F809S	0.999
3:155488740:C:G	R808P	0.999

dbSNP variants (sampled 300 via entrez): RS1000016074 (3:155621600 A>G,T), RS1000037710 (3:155610376 AAAAAAAAAAAAAAC>A), RS1000042532 (3:155661047 T>C), RS1000048366 (3:155678235 C>T), RS1000054256 (3:155632261 A>G), RS1000056192 (3:155654743 T>A,C), RS1000098648 (3:155616560 G>C), RS1000106197 (3:155608998 T>C,G), RS1000123217 (3:155488648 G>C), RS1000125141 (3:155522783 A>G), RS1000133376 (3:155471853 G>A), RS1000136251 (3:155565393 C>T), RS1000141560 (3:155539083 T>C), RS1000150449 (3:155560786 C>T), RS1000160398 (3:155604137 T>C,G)

Disease associations

OMIM: gene MIM:612835 | disease phenotypes: MIM:619895

GenCC curated gene-disease

Disease	Classification	Inheritance
holoprosencephaly 14	Strong	Autosomal recessive

Mondo (1): holoprosencephaly 14 (MONDO:0030886)

Orphanet (0):

HPO phenotypes

101 total (30 of 101 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000119	Abnormality of the genitourinary system
HP:0000161	Median cleft upper lip
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000407	Sensorineural hearing impairment
HP:0000457	Depressed nasal ridge
HP:0000463	Anteverted nares
HP:0000478	Abnormality of the eye
HP:0000601	Hypotelorism
HP:0000708	Atypical behavior
HP:0000716	Depression
HP:0000737	Irritability
HP:0000739	Anxiety
HP:0000741	Apathy
HP:0000818	Abnormality of the endocrine system
HP:0000824	Decreased response to growth hormone stimulation test
HP:0000871	Panhypopituitarism
HP:0000873	Diabetes insipidus
HP:0000924	Abnormality of the skeletal system
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001254	Lethargy
HP:0001257	Spasticity

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012489_15	Heel bone mineral density x serum urate levels interaction	6.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Phosphoinositide-specific phospholipase C

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, decreases methylation, increases expression	6
trichostatin A	affects cotreatment, decreases expression, increases expression	3
bisphenol A	affects cotreatment, increases methylation, decreases methylation, increases expression	2
entinostat	decreases expression, affects cotreatment	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Tobacco Smoke Pollution	decreases expression, affects expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	affects methylation	1
butyraldehyde	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression	1
pentanal	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
Grape Seed Proanthocyanidins	decreases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	decreases methylation	1
Temozolomide	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Calcitriol	decreases expression, affects cotreatment	1
Catechin	affects cotreatment, decreases expression	1
Cytarabine	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Formaldehyde	decreases expression	1
Progesterone	decreases expression	1
Silicon Dioxide	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TE40	HAP1 PLCH1 (-) 1	Cancer cell line	Male
CVCL_TE41	HAP1 PLCH1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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