PLEKHA5

Summary

PLEKHA5 (pleckstrin homology domain containing A5, HGNC:30036) is a protein-coding gene on chromosome 12p12.3, encoding Pleckstrin homology domain-containing family A member 5 (Q9HAU0).

Predicted to enable phosphatidylinositol phosphate binding activity. Predicted to act upstream of or within reproductive system development. Located in cytosol and nucleoplasm.

Source: NCBI Gene 54477 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cleft lip/palate (Moderate, GenCC)
• GWAS associations: 10
• Clinical variants (ClinVar): 193 total — 1 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_001256470

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30036
Approved symbol	PLEKHA5
Name	pleckstrin homology domain containing A5
Location	12p12.3
Locus type	gene with protein product
Status	Approved
Aliases	PEPP2, KIAA1686, FLJ10667
Ensembl gene	ENSG00000052126
Ensembl biotype	protein_coding
OMIM	607770
Entrez	54477

Gene structure

Transcript identifiers

Ensembl transcripts: 70 — 39 protein_coding, 20 retained_intron, 6 protein_coding_CDS_not_defined, 5 nonsense_mediated_decay

ENST00000299275, ENST00000424268, ENST00000429027, ENST00000510738, ENST00000534979, ENST00000535357, ENST00000536974, ENST00000537027, ENST00000538034, ENST00000538068, ENST00000538305, ENST00000538677, ENST00000538714, ENST00000538972, ENST00000539256, ENST00000540972, ENST00000700680, ENST00000700681, ENST00000700682, ENST00000700683, ENST00000700684, ENST00000700685, ENST00000700686, ENST00000700687, ENST00000700688, ENST00000700689, ENST00000700691, ENST00000700692, ENST00000700693, ENST00000700694, ENST00000700695, ENST00000706613, ENST00000706614, ENST00000706615, ENST00000706616, ENST00000706617, ENST00000706618, ENST00000706619, ENST00000706620, ENST00000706621, ENST00000706622, ENST00000706623, ENST00000706624, ENST00000874831, ENST00000874832, ENST00000874833, ENST00000874834, ENST00000874835, ENST00000930145, ENST00000930146, ENST00000930147, ENST00000930148, ENST00000930149, ENST00000930150, ENST00000930151, ENST00000930152, ENST00000930153, ENST00000930154, ENST00000930155, ENST00000930156, ENST00000954862, ENST00000954863, ENST00000954864, ENST00000954865, ENST00000954866, ENST00000954867, ENST00000954868, ENST00000954869, ENST00000954870, ENST00000954871

RefSeq mRNA: 56 — MANE Select: NM_001256470 NM_001143821, NM_001190860, NM_001256470, NM_001256787, NM_001385923, NM_001385924, NM_001385925, NM_001385926, NM_001385927, NM_001385928, NM_001385929, NM_001385930, NM_001385931, NM_001385932, NM_001385933, NM_001385934, NM_001385935, NM_001385936, NM_001385937, NM_001385938, NM_001385939, NM_001385940, NM_001385941, NM_001385942, NM_001385943, NM_001385944, NM_001385945, NM_001385946, NM_001385947, NM_001385948, NM_001385949, NM_001385950, NM_001385951, NM_001385952, NM_001385953, NM_001385954, NM_001385955, NM_001385956, NM_001385957, NM_001385958, NM_001385959, NM_001385960, NM_001385961, NM_001385962, NM_001385963, NM_001385964, NM_001385965, NM_001385966, NM_001385967, NM_001385968, NM_001385969, NM_001385970, NM_001385971, NM_001385972, NM_001385973, NM_019012

CCDS: CCDS44840, CCDS55809, CCDS58213, CCDS58214, CCDS8682, CCDS91659, CCDS91660

Canonical transcript exons

ENST00000429027 — 32 exons

Exon	Start	End
ENSE00001159952	19358228	19358437
ENSE00001209111	19365964	19366109
ENSE00001209133	19353884	19354002
ENSE00001209193	19369693	19369798
ENSE00001276656	19346994	19347182
ENSE00001276766	19348399	19348519
ENSE00001295918	19291644	19291697
ENSE00001311810	19359412	19359546
ENSE00001318648	19290677	19290796
ENSE00001742144	19270188	19270205
ENSE00001775395	19314814	19314894
ENSE00002219377	19129733	19129888
ENSE00002251041	19375531	19376400
ENSE00002275584	19283280	19283745
ENSE00002692964	19361582	19361706
ENSE00003602229	19320021	19320056
ENSE00003996324	19343323	19343434
ENSE00003996327	19130051	19130130
ENSE00003996328	19274516	19274983
ENSE00003996331	19253940	19254023
ENSE00003996333	19255045	19255165
ENSE00003996334	19345842	19345888
ENSE00003996335	19257433	19257537
ENSE00003996337	19265750	19265850
ENSE00003996339	19336515	19336616
ENSE00003996348	19322310	19322390
ENSE00003996349	19269770	19269885
ENSE00003996350	19287473	19287556
ENSE00003996357	19260949	19261021
ENSE00003996360	19322518	19322667
ENSE00003996362	19132393	19132450
ENSE00003996366	19320562	19320624

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 97.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.8775 / max 560.3382, expressed in 1707 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
124570	13.0891	1592
124580	5.1293	479
124569	1.3464	786
124567	1.1182	629
124571	0.9498	449
124568	0.5531	302
124577	0.2775	74
124581	0.1650	50
124576	0.1454	57
124579	0.0542	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of paranasal sinus	UBERON:0005030	97.77	gold quality
buccal mucosa cell	CL:0002336	97.47	gold quality
bronchial epithelial cell	CL:0002328	96.31	gold quality
endometrium	UBERON:0001295	95.81	gold quality
caput epididymis	UBERON:0004358	95.76	gold quality
renal medulla	UBERON:0000362	95.67	gold quality
corpus epididymis	UBERON:0004359	95.48	gold quality
epithelium of bronchus	UBERON:0002031	95.42	gold quality
right adrenal gland	UBERON:0001233	95.36	gold quality
bronchus	UBERON:0002185	95.27	gold quality
cauda epididymis	UBERON:0004360	95.02	gold quality
left adrenal gland	UBERON:0001234	94.89	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.86	gold quality
adrenal tissue	UBERON:0018303	94.83	gold quality
adrenal cortex	UBERON:0001235	94.81	gold quality
left adrenal gland cortex	UBERON:0035825	94.73	gold quality
seminal vesicle	UBERON:0000998	94.46	gold quality
calcaneal tendon	UBERON:0003701	94.44	gold quality
periodontal ligament	UBERON:0008266	94.40	gold quality
adrenal gland	UBERON:0002369	94.34	gold quality
right adrenal gland cortex	UBERON:0035827	94.32	gold quality
tongue squamous epithelium	UBERON:0006919	94.24	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.82	gold quality
urethra	UBERON:0000057	93.79	gold quality
lower esophagus mucosa	UBERON:0035834	93.69	gold quality
pylorus	UBERON:0001166	93.60	gold quality
endothelial cell	CL:0000115	93.53	gold quality
pigmented layer of retina	UBERON:0001782	93.51	gold quality
cranial nerve II	UBERON:0000941	93.19	gold quality
epithelium of nasopharynx	UBERON:0001951	92.99	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-GEOD-75688	yes	2061.90
E-MTAB-6108	yes	206.44
E-MTAB-10287	yes	109.42
E-HCAD-35	yes	96.50
E-CURD-119	yes	53.98
E-GEOD-135922	yes	28.21
E-CURD-112	yes	13.54
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

74 targeting PLEKHA5, 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-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-424-5P	99.89	71.90	2641

Literature-anchored findings (GeneRIF, showing 4)

• PLEKHA5 expression in melanoma tumors was associated with early development of brain metastases (PMID:25316811)
• High genetic risk scores of SLIT3, PLEKHA5 and PPP2R2C variants increase susceptibility to increased insulin resistance by 50% and its risk may be exacerbated by consuming more than 10 cups coffee/week or 220 mg caffeine/day. (PMID:30454882)
• PLEKHA5 regulates tumor growth in metastatic melanoma. (PMID:31769872)
• PLEKHA5, PLEKHA6, and PLEKHA7 bind to PDZD11 to target the Menkes ATPase ATP7A to the cell periphery and regulate copper homeostasis. (PMID:34613798)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	plekha5	ENSDARG00000045870
mus_musculus	Plekha5	ENSMUSG00000030231
rattus_norvegicus	Plekha5	ENSRNOG00000008747

Paralogs (3): PLEKHA4 (ENSG00000105559), PLEKHA6 (ENSG00000143850), PLEKHA7 (ENSG00000166689)

Protein

Protein identifiers

Pleckstrin homology domain-containing family A member 5 — Q9HAU0 (reviewed: Q9HAU0)

Alternative names: Phosphoinositol 3-phosphate-binding protein 2

All UniProt accessions (12): A0A8V8TQ09, A0A8V8TQJ6, A0A8V8TQJ8, Q9HAU0, A0A8V8TR40, A0A8V8TRE5, A0A9L9PX43, B4DJX4, F5H1X3, F6VRM0, H0YG48, H0YGJ6

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm.

Tissue specificity. Highly expressed in heart and kidney.

Domain organisation. Specifically interacts with PI3P, PI4P, PI5P, and PI(3,5)P2.

Miscellaneous. Specifically expressed in brain.

Isoforms (8)

UniProt ID	Names	Canonical?
Q9HAU0-1	1, S	yes
Q9HAU0-2	2
Q9HAU0-3	3
Q9HAU0-4	4
Q9HAU0-5	5
Q9HAU0-6	6, L
Q9HAU0-7	7
Q9HAU0-8	8

RefSeq proteins (56): NP_001137293, NP_001177789, NP_001243399, NP_001243716, NP_001372852, NP_001372853, NP_001372854, NP_001372855, NP_001372856, NP_001372857, NP_001372858, NP_001372859, NP_001372860, NP_001372861, NP_001372862, NP_001372863, NP_001372864, NP_001372865, NP_001372866, NP_001372867, NP_001372868, NP_001372869, NP_001372870, NP_001372871, NP_001372872, NP_001372873, NP_001372874, NP_001372875, NP_001372876, NP_001372877, NP_001372878, NP_001372879, NP_001372880, NP_001372881, NP_001372882, NP_001372883, NP_001372884, NP_001372885, NP_001372886, NP_001372887, NP_001372888, NP_001372889, NP_001372890, NP_001372891, NP_001372892, NP_001372893, NP_001372894, NP_001372895, NP_001372896, NP_001372897, NP_001372898, NP_001372899, NP_001372900, NP_001372901, NP_001372902, NP_061885 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001202	WW_dom	Domain
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR036020	WW_dom_sf	Homologous_superfamily
IPR040392	PKHA4-7_PH	Domain
IPR057971	PKHA4-7_TBCA	Domain

Pfam: PF00169, PF00397, PF25541

UniProt features (57 total): modified residue 12, splice variant 10, strand 9, compositionally biased region 8, sequence conflict 5, region of interest 4, domain 3, helix 3, initiator methionine 1, chain 1, cross-link 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2DKP	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HAU0-F1	55.77	0.18

Functional residue map

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

Post-translational modifications (13): 2, 55, 382, 410, 438, 460, 568, 607, 809, 855, 933, 937, 301

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1660499	Synthesis of PIPs at the plasma membrane

MSigDB gene sets: 239 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, WENDT_COHESIN_TARGETS_UP, FREAC2_01, GOLDRATH_IMMUNE_MEMORY, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, ATGTTAA_MIR302C, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, FREAC3_01, GOBP_REPRODUCTIVE_SYSTEM_DEVELOPMENT, FISCHER_G2_M_CELL_CYCLE, RUTELLA_RESPONSE_TO_HGF_VS_CSF2RB_AND_IL4_DN, JAATINEN_HEMATOPOIETIC_STEM_CELL_UP, RIGGINS_TAMOXIFEN_RESISTANCE_DN, SCHLINGEMANN_SKIN_CARCINOGENESIS_TPA_DN

GO Biological Process (1): reproductive system development (GO:0061458)

GO Molecular Function (5): phosphatidylinositol-5-phosphate binding (GO:0010314), phosphatidylinositol-3-phosphate binding (GO:0032266), phosphatidylinositol-4-phosphate binding (GO:0070273), phosphatidylinositol-3,5-bisphosphate binding (GO:0080025), protein binding (GO:0005515)

GO Cellular Component (6): nucleoplasm (GO:0005654), cytosol (GO:0005829), postsynaptic density (GO:0014069), membrane (GO:0016020), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
PI Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphatidylinositol phosphate binding	4
cellular anatomical structure	4
anion binding	2
system development	1
phosphatidylinositol bisphosphate binding	1
binding	1
nuclear lumen	1
cytoplasm	1
asymmetric synapse	1
postsynaptic specialization	1
synapse	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1054 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLEKHA5	PLEK2	Q9NYT0	579
PLEKHA5	PLEK	P08567	571
PLEKHA5	ACTR10	Q9NZ32	529
PLEKHA5	NUDT4B	A0A024RBG1	494
PLEKHA5	MPHOSPH8	Q99549	494
PLEKHA5	PDZD11	Q5EBL8	467
PLEKHA5	SLC15A5	A6NIM6	455
PLEKHA5	ADGRA1	Q86SQ6	435
PLEKHA5	AEBP2	Q6ZN18	434
PLEKHA5	FRMD4B	Q9Y2L6	425
PLEKHA5	EIF2S3	P41091	419
PLEKHA5	TMEM260	Q9NX78	398
PLEKHA5	ARHGAP31	Q2M1Z3	387
PLEKHA5	MEIG1	Q5JSS6	382
PLEKHA5	NUSAP1	Q9BXS6	379

IntAct

190 interactions, top by confidence:

A	B	Type	Score
PIK3CA	PIK3R2	psi-mi:“MI:0914”(association)	0.900
PLEKHA5	PDZD11	psi-mi:“MI:0915”(physical association)	0.720
PDZD11	PLEKHA5	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PLEKHA5	rep	psi-mi:“MI:0915”(physical association)	0.660
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
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
YWHAB	BLTP3B	psi-mi:“MI:0914”(association)	0.610
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
SLC16A3	CASK	psi-mi:“MI:0914”(association)	0.590
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
rep	SBNO1	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
FHL2	CNOT1	psi-mi:“MI:0914”(association)	0.530
PPP2R5A	AXIN1	psi-mi:“MI:0914”(association)	0.530
ZNRD2	MYO9A	psi-mi:“MI:0914”(association)	0.530
GINM1	ADCY9	psi-mi:“MI:0914”(association)	0.530
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.530

BioGRID (296): PLEKHA5 (Two-hybrid), PLEKHA5 (Affinity Capture-MS), PLEKHA5 (Affinity Capture-MS), PLEKHA5 (Biochemical Activity), PLEKHA5 (Proximity Label-MS), PLEKHA5 (Proximity Label-MS), PLEKHA5 (Proximity Label-MS), PLEKHA5 (Proximity Label-MS), PLEKHA5 (Proximity Label-MS), PLEKHA5 (Proximity Label-MS), PLEKHA5 (Affinity Capture-MS), PLEKHA5 (Affinity Capture-MS), PLEKHA5 (Affinity Capture-MS), PLEKHA5 (Affinity Capture-MS), PLEKHA5 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JTY4, A0JNC2, A2AQ25, E1BEQ5, O09000, O57539, O70305, O93602, P15336, P16951, P17544, P70365, P97305, Q00969, Q02930, Q12968, Q14157, Q15032, Q15596, Q15788, Q1LY51, Q4PJW2, Q4VCS5, Q5R9C9, Q5SFM8, Q5T5P2, Q5T6F2, Q61026, Q62415, Q6GP15, Q80TM6, Q80X50, Q86YP4, Q8CHY6, Q8IY63, Q8VCB2, Q8VHG2, Q8VHR5, Q8WXI9, Q91VX2

Diamond homologs: B6RSP1, D3ZL52, G9CGD6, O08967, O43739, P54644, P60669, P97434, P97696, Q3UIL6, Q5DU31, Q6IQ23, Q6WCQ1, Q6ZNL6, Q7TQG1, Q80UZ0, Q80VL0, Q80YA9, Q86IV4, Q8BH49, Q8C4V1, Q8N264, Q8N4B1, Q8VC98, Q8WWN9, Q8WXI2, Q99KW3, Q9ERE6, Q9ERS5, Q9H4M7, Q9HAU0, Q9HB19, Q9Y2H5, Q9Z1T4, A8JQ65, B3LXF2, B3NYS4, B4I4Y1, B4JHJ7, B4K6T8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 184 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	46.3×	5e-09
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	40.9×	1e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	40.9×	1e-08
Activation of BH3-only proteins	8	34.5×	4e-09
Nephrin family interactions	5	20.7×	1e-04
RAF activation	7	20.4×	2e-06
Intrinsic Pathway for Apoptosis	8	20.4×	2e-07
RHO GTPases activate PKNs	7	19.3×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	7	16.1×	1e-04
non-motile cilium assembly	6	11.0×	5e-03
intracellular protein localization	13	8.6×	5e-06
cilium assembly	11	5.1×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	130
Likely benign	19
Benign	7

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
4070968	NM_001256470.2(PLEKHA5):c.185G>A (p.Trp62Ter)	Pathogenic
834028	NM_001256470.2(PLEKHA5):c.1787A>G (p.Tyr596Cys)	Likely pathogenic

SpliceAI

6099 predictions. Top by Δscore:

Variant	Effect	Δscore
12:19129889:G:GG	donor_gain	1.0000
12:19129902:G:T	donor_gain	1.0000
12:19132387:TTTTA:T	acceptor_loss	1.0000
12:19132388:TTTA:T	acceptor_loss	1.0000
12:19132391:A:AG	acceptor_gain	1.0000
12:19132391:AG:A	acceptor_loss	1.0000
12:19132392:G:A	acceptor_loss	1.0000
12:19132392:G:GG	acceptor_gain	1.0000
12:19132392:GATTT:G	acceptor_gain	1.0000
12:19132451:G:GG	donor_gain	1.0000
12:19174646:GGC:G	donor_gain	1.0000
12:19253938:A:AG	acceptor_gain	1.0000
12:19253939:G:GG	acceptor_gain	1.0000
12:19253939:GC:G	acceptor_gain	1.0000
12:19253939:GCC:G	acceptor_gain	1.0000
12:19253939:GCCA:G	acceptor_gain	1.0000
12:19253939:GCCAT:G	acceptor_gain	1.0000
12:19253995:G:GT	donor_gain	1.0000
12:19254019:GAACA:G	donor_gain	1.0000
12:19254020:AACA:A	donor_gain	1.0000
12:19254021:ACA:A	donor_gain	1.0000
12:19254022:CA:C	donor_gain	1.0000
12:19254023:AG:A	donor_loss	1.0000
12:19254024:G:GG	donor_gain	1.0000
12:19254026:AA:A	donor_loss	1.0000
12:19255039:TTTCA:T	acceptor_loss	1.0000
12:19255040:TTCA:T	acceptor_loss	1.0000
12:19255042:CA:C	acceptor_loss	1.0000
12:19255043:A:AG	acceptor_gain	1.0000
12:19255043:AG:A	acceptor_gain	1.0000

AlphaMissense

8436 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:19129845:T:A	W16R	1.000
12:19129845:T:C	W16R	1.000
12:19129882:T:C	F28S	1.000
12:19130073:T:A	W38R	1.000
12:19130073:T:C	W38R	1.000
12:19130077:T:C	L39P	1.000
12:19130083:C:A	P41H	1.000
12:19132407:T:A	W62R	1.000
12:19132407:T:C	W62R	1.000
12:19132409:G:C	W62C	1.000
12:19132409:G:T	W62C	1.000
12:19257463:T:C	F155L	1.000
12:19257464:T:C	F155S	1.000
12:19257464:T:G	F155C	1.000
12:19257465:T:A	F155L	1.000
12:19257465:T:G	F155L	1.000
12:19257466:G:A	G156R	1.000
12:19257466:G:C	G156R	1.000
12:19257467:G:A	G156E	1.000
12:19257467:G:T	G156V	1.000
12:19257469:A:G	K157E	1.000
12:19257471:G:C	K157N	1.000
12:19257471:G:T	K157N	1.000
12:19257473:G:C	R158T	1.000
12:19257473:G:T	R158M	1.000
12:19257474:G:C	R158S	1.000
12:19257474:G:T	R158S	1.000
12:19257491:G:C	R164T	1.000
12:19257491:G:T	R164M	1.000
12:19257492:G:C	R164S	1.000

dbSNP variants (sampled 300 via entrez): RS1000002598 (12:19220883 G>A), RS1000014455 (12:19158499 A>T), RS1000026937 (12:19272111 C>T), RS1000033146 (12:19234966 T>C), RS1000037910 (12:19362736 G>A,T), RS1000042966 (12:19255247 A>G), RS1000066711 (12:19146457 G>A), RS1000067955 (12:19221168 C>T), RS1000083357 (12:19188299 T>G), RS1000093797 (12:19173368 T>C,G), RS1000094840 (12:19255004 A>G), RS1000100500 (12:19153900 C>A), RS1000117158 (12:19315317 T>C), RS1000125773 (12:19306585 GC>G), RS1000141107 (12:19362941 A>G)

Disease associations

OMIM: gene MIM:607770 | disease phenotypes: MIM:143890

GenCC curated gene-disease

Disease	Classification	Inheritance
cleft lip/palate	Moderate	Autosomal dominant

Mondo (2): hypercholesterolemia, familial, 1 (MONDO:0007750), cleft lip/palate (MONDO:0016044)

Orphanet (2): Homozygous familial hypercholesterolemia (Orphanet:391665), Cleft lip with or without cleft palate (Orphanet:1991)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002887_2	Pharmacokinetics of antiepileptic drugs in severe mental disorder (concentration drug ratio)	1.000000e-07
GCST003518_20	Daytime sleep phenotypes	2.000000e-06
GCST003855_9	Gut microbiota (bacterial taxa)	1.000000e-08
GCST008708_3	Chronic mountain sickness	5.000000e-09
GCST009264_12	Thalamus volume	7.000000e-07
GCST010397_37	Gut microbiota (bacterial taxa, rank normal transformation method)	2.000000e-06
GCST010485_16	Platelet reactivity in response to clopidogrel treatment	7.000000e-06
GCST010988_488	Adult body size	1.000000e-09
GCST90000047_175	Age at first sexual intercourse	7.000000e-10
GCST90000047_176	Age at first sexual intercourse	2.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007635	concentration dose ratio
EFO:0007828	daytime rest measurement
EFO:0007874	gut microbiome measurement
EFO:0010143	chronic mountain sickness
EFO:0006935	thalamus volume
EFO:0009749	age at first sexual intercourse measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, increases expression	5
Benzo(a)pyrene	decreases expression, affects methylation	3
bisphenol A	affects methylation, decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, decreases reaction	1
methylparaben	decreases expression	1
sodium arsenite	decreases expression, increases abundance	1
cobaltous chloride	decreases expression	1
zinc chromate	increases abundance, increases expression	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
aflatoxin B2	decreases methylation	1
coumarin	increases phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
incobotulinumtoxinA	increases expression	1
Irinotecan	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Vorinostat	decreases expression	1
Vehicle Emissions	affects expression, increases abundance	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C9B6	CLF_PEDS9001_T1	Cancer cell line

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04234971	PHASE4	RECRUITING	Cost Effectiveness in Alveolar Bone Grafting in Patients With Cleft Lip and Palate
NCT04771156	PHASE4	RECRUITING	Ketorolac in Palatoplasty
NCT06231459	PHASE4	COMPLETED	Expression of Pro- and Anti-inflammatory Cytokines During Anti-PCSK9 in Familial Hypercholesterolemia
NCT03766217	PHASE3	COMPLETED	Bone Tissue Engineering With Dental Pulp Stem Cells for Alveolar Cleft Repair
NCT06284434	PHASE3	RECRUITING	Liposomal Bupivacaine Use in Alveolar Bone Graft Patients
NCT00000594	PHASE3	COMPLETED	NHLBI Type II Coronary Intervention Study
NCT00092833	PHASE3	TERMINATED	Investigational Drug in Patients With Hypercholesterolemia or in Patients With Sitosterolemia (0653-026)(COMPLETED)
NCT00134485	PHASE3	COMPLETED	Study To Evaluate The Safety And Efficacy Of Torcetrapib/Atorvastatin In Subjects With Familial Hypercholerolemia
NCT00134511	PHASE3	COMPLETED	Study To Evaluate The Effect Of Torcetrapib/Atorvastatin In Patients With Genetic High Cholesterol Disorder
NCT00136981	PHASE3	COMPLETED	Carotid B-Mode Ultrasound Study to Compare Anti-Atherosclerotic Effect of Torcetrpib/Atorvastatin to Atorvastatin Alone.
NCT00384293	PHASE3	TERMINATED	Carotid IMT (Intima Media Thickening) Study (0524A-041)(TERMINATED)
NCT01524289	PHASE3	COMPLETED	Study to Assess the Tolerability and Efficacy of Anacetrapib (MK-0859) Co-Administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020)
NCT00930124	PHASE2	COMPLETED	Cleft Orthognathic Surgery Versus Distraction Osteogenesis - Which is Better?
NCT00280995	PHASE2	COMPLETED	Dose-escalating Safety Study of ISIS 301012 in Homozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT00281008	PHASE2	COMPLETED	Study of ISIS 301012 (Mipomersen) in Heterozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT01375751	PHASE2	COMPLETED	Reduction of Low-Density Lipoprotein Cholesterol (LDL-C) With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study
NCT00515307	PHASE1	COMPLETED	Bone Marrow Stem Cells as a Source of Allogenic Hepatocyte Transplantation in Homozygous Familial Hypercholesterolemia
NCT01583647	PHASE1	TERMINATED	A Study of Extended-release (ER) Niacin/Laropiprant in Adolescents With Heterozygous Familial Hypercholesterolemia (MK-0524A-158)
NCT06408337	PHASE1/PHASE2	RECRUITING	Phase I-IIa, to Evaluate the Safety, Feasibility, and Efficacy of the Use of BIOCLEFT in the Treatment of Cleft Palate.
NCT00070811	Not specified	COMPLETED	Assessing the Results of Lip Surgery in Patients With Cleft Lip and Palate
NCT00156442	Not specified	COMPLETED	A Study to Examine the Relationship Between Sleep Apnea and Cleft Lip/Palate
NCT01601171	Not specified	RECRUITING	Genetics of Reproductive Disorders (Including Kallmann Syndrome) and Cleft Lip and/or Palate
NCT01871623	Not specified	UNKNOWN	One-Piece Le Fort I Osteotomy Versus Segmental Le Fort I Osteotomy
NCT01932164	Not specified	COMPLETED	Use of Mesenchymal Stem Cells for Alveolar Bone Tissue Engineering for Cleft Lip and Palate Patients
NCT02702869	Not specified	ENROLLING_BY_INVITATION	Allied Cleft & Craniofacial Quality-Improvement and Research Network (ACCQUIREnet)
NCT02789787	Not specified	COMPLETED	Clinical Effectiveness of Late Maxillary Protraction for Cleft Lip and Palate
NCT02845193	Not specified	COMPLETED	Effect of Novel Nasoalveolar Molding Techniques on Parents’ Satisfaction and Short Term Treatment Outcomes in Unilateral Cleft Lip and Palate Infants: A Randomized Controlled Trial
NCT02881606	Not specified	COMPLETED	Evaluation of the Clinical Effectiveness of Naso-alveolar Molding (NAM) Versus Computer Aided Design NAM (CAD/NAM) in Infants With Bilateral Cleft Lip and Palate: A Randomized Clinical Trial
NCT03011489	Not specified	UNKNOWN	Parent’s Satisfaction and Evaluation of Postsurgical Outcomes in Unilateral Cleft Lip / Palate Newly Born Infants With / Without Vacuum Formed Nasoalveolar Molding Aligners : A Controlled Clinical Trial
NCT03065686	Not specified	RECRUITING	Identification of Genetic Factors Implicated in Orofacial Cleft Using Whole Exome Sequencing
NCT03165331	Not specified	UNKNOWN	Online Psychosocial Support for Young People With a Visible Difference: A Randomised Control Study
NCT03217890	Not specified	UNKNOWN	the Relationship Between Cleft Lip and / or Palate (Different Types) and ABO Blood Groups.
NCT03308266	Not specified	COMPLETED	Electromyographic Analysis of the Masticatory Muscles in Cleft Lip and Palate Children With Temporomandibular Disorders
NCT03395015	Not specified	COMPLETED	Efficacy of Maxillo-facial Treatment on Cleft Lip and Palate Patients Faces: Aesthetic Considerations
NCT03514563	Not specified	TERMINATED	Three Dimensional Facial Growth Analysis
NCT03563495	Not specified	COMPLETED	Tissue Engineered Constructs for Alveolar Cleft Repair
NCT03582111	Not specified	COMPLETED	Ultrasound Diagnosis of Cleft Lip and Palate
NCT03686761	Not specified	COMPLETED	Periodontal Changes Following Mid Maxillary Distraction
NCT03708406	Not specified	COMPLETED	Otologic and Rhinologic Outcomes in Children With Clef Palate
NCT03740841	Not specified	TERMINATED	Evaluation of the Effects of LUNII on Pre-operative Anxiety and on the Post-operative Period in Children With Cleft Lip and Palate Admitted for Alveolar Bone Graft: Pilot Study