PKD1L1

Summary

PKD1L1 (polycystin 1 like 1, transient receptor potential channel interacting, HGNC:18053) is a protein-coding gene on chromosome 7p12.3, encoding Polycystin-1-like protein 1 (Q8TDX9). Component of a calcium-permeant ion channel formed by PKD1L2 and PKD1L1 in primary cilia, where it controls cilium calcium concentration, without affecting cytoplasmic calcium concentration, and regulates sonic hedgehog/SHH signaling and GLI2 transcription.

This gene encodes a member of the polycystin protein family containing 11 transmembrane domains, a receptor for egg jelly (REJ) domain, and a polycystin-1, lipoxygenase, alpha-toxin (PLAT) domain. The encoded protein may play a role in the male reproductive system. Alternative splice variants have been described but their biological nature has not been determined.

Source: NCBI Gene 168507 — RefSeq curated summary.

At a glance

• Gene–disease (curated): heterotaxy, visceral, 8, autosomal (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 8
• Clinical variants (ClinVar): 1,179 total — 26 pathogenic, 32 likely-pathogenic
• Phenotypes (HPO): 14
• MANE Select transcript: NM_138295

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18053
Approved symbol	PKD1L1
Name	polycystin 1 like 1, transient receptor potential channel interacting
Location	7p12.3
Locus type	gene with protein product
Status	Approved
Aliases	PRO19563
Ensembl gene	ENSG00000158683
Ensembl biotype	protein_coding
OMIM	609721
Entrez	168507

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000289672, ENST00000433506, ENST00000462350, ENST00000483616, ENST00000648482, ENST00000685709, ENST00000686775, ENST00000690269

RefSeq mRNA: 1 — MANE Select: NM_138295 NM_138295

CCDS: CCDS34633

Canonical transcript exons

ENST00000289672 — 57 exons

Exon	Start	End
ENSE00001040309	47808247	47808387
ENSE00001040310	47803210	47803344
ENSE00001040316	47809473	47809577
ENSE00001040322	47800649	47800879
ENSE00001137078	47795989	47796150
ENSE00001137148	47827350	47827468
ENSE00001137155	47829425	47829601
ENSE00001137160	47830040	47830124
ENSE00001137166	47831217	47831352
ENSE00001137173	47833090	47833252
ENSE00001137179	47834339	47834385
ENSE00001137186	47834967	47835039
ENSE00001137191	47835133	47835243
ENSE00001137197	47836921	47837094
ENSE00001137201	47839446	47839662
ENSE00001137207	47840461	47840567
ENSE00001137213	47842962	47843169
ENSE00001137220	47844995	47845078
ENSE00001137225	47846879	47847071
ENSE00001137231	47853127	47853227
ENSE00001137237	47854882	47855039
ENSE00001137244	47855155	47855265
ENSE00001137251	47857605	47857832
ENSE00001137255	47858673	47858885
ENSE00001137261	47865216	47865272
ENSE00001137268	47866419	47866614
ENSE00001137272	47873899	47874010
ENSE00001137280	47876097	47876217
ENSE00001137285	47877489	47877631
ENSE00001137289	47880728	47880805
ENSE00001137294	47881909	47882085
ENSE00001137300	47884598	47884657
ENSE00001137305	47885686	47886054
ENSE00001137312	47887990	47888150
ENSE00001137319	47890542	47890763
ENSE00001137326	47893878	47894059
ENSE00001137330	47897988	47898194
ENSE00001137338	47902379	47902511
ENSE00001137344	47904378	47904617
ENSE00001137349	47905157	47905325
ENSE00001137356	47905843	47905962
ENSE00001137363	47908077	47908250
ENSE00001137371	47915432	47915599
ENSE00001137376	47929204	47929526
ENSE00001137384	47931104	47931321
ENSE00001137392	47931936	47932056
ENSE00001137398	47936846	47936958
ENSE00001137402	47940193	47940317
ENSE00001137407	47943396	47943511
ENSE00001175557	47792627	47792797
ENSE00001175559	47948397	47948466
ENSE00001274033	47774614	47775166
ENSE00003534639	47821076	47821186
ENSE00003546706	47813121	47813293
ENSE00003570006	47811817	47812051
ENSE00003620218	47813931	47814014
ENSE00003642682	47815334	47815457

Expression profiles

Bgee: expression breadth ubiquitous, 150 present calls, max score 76.48.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2457 / max 17.4780, expressed in 105 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
84067	0.1993	94
84068	0.0464	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.48	gold quality
apex of heart	UBERON:0002098	75.25	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	73.57	gold quality
lower esophagus mucosa	UBERON:0035834	69.31	gold quality
heart left ventricle	UBERON:0002084	69.05	gold quality
cardiac ventricle	UBERON:0002082	68.15	gold quality
left testis	UBERON:0004533	66.50	gold quality
hindlimb stylopod muscle	UBERON:0004252	65.98	gold quality
colonic epithelium	UBERON:0000397	65.16	gold quality
testis	UBERON:0000473	64.25	gold quality
right testis	UBERON:0004534	63.61	gold quality
heart	UBERON:0000948	63.49	gold quality
muscle of leg	UBERON:0001383	63.46	gold quality
gastrocnemius	UBERON:0001388	62.37	gold quality
right atrium auricular region	UBERON:0006631	62.23	gold quality
cardiac atrium	UBERON:0002081	61.67	gold quality
omental fat pad	UBERON:0010414	60.56	gold quality
peritoneum	UBERON:0002358	60.51	gold quality
ventricular zone	UBERON:0003053	60.44	gold quality
adipose tissue of abdominal region	UBERON:0007808	59.47	gold quality
lower esophagus	UBERON:0013473	59.24	gold quality
lower esophagus muscularis layer	UBERON:0035833	59.15	gold quality
subcutaneous adipose tissue	UBERON:0002190	58.17	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	56.53	gold quality
lymph node	UBERON:0000029	56.04	gold quality
nucleus accumbens	UBERON:0001882	55.26	gold quality
upper lobe of left lung	UBERON:0008952	55.23	gold quality
adipose tissue	UBERON:0001013	54.96	gold quality
mucosa of transverse colon	UBERON:0004991	54.95	gold quality
right coronary artery	UBERON:0001625	54.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.05

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting PKD1L1, 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-513B-5P	99.99	69.96	2150
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-3606-3P	99.11	69.84	3254
HSA-MIR-622	98.99	66.48	1050
HSA-MIR-887-5P	98.82	65.90	1347
HSA-MIR-541-5P	98.24	67.77	1181
HSA-MIR-33B-3P	97.92	67.39	529
HSA-MIR-515-3P	97.92	67.98	506
HSA-MIR-519E-3P	97.92	68.25	508
HSA-MIR-4288	97.11	67.23	1636
HSA-MIR-4793-5P	96.88	65.90	872
HSA-MIR-4433A-5P	96.79	65.01	599

Literature-anchored findings (GeneRIF, showing 3)

• The authors report that the human PKD2-L1 selectivity filter is partially selective to calcium ions (Ca(2+)) moving into the cell, but blocked by high internal Ca(2+)concentrations, a unique feature of this transient receptor potential (TRP) channel family member. (PMID:27348301)
• identification of bi-allelic PKD1L1 mutations recapitulates previous findings regarding phenotypic consequences of loss of function of the orthologous genes in mice and medaka fish and further expands our understanding of genetic contributions to laterality defects in humans (PMID:27616478)
• PKD1L1 Is Involved in Congenital Chylothorax. (PMID:38247840)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pkd1l1	ENSMUSG00000046634
rattus_norvegicus	Pkd1l1	ENSRNOG00000004865
drosophila_melanogaster	Pkd2	FBGN0041195
caenorhabditis_elegans		WBGENE00004035

Paralogs (10): PKD1 (ENSG00000008710), PKD2L2 (ENSG00000078795), PKD2L1 (ENSG00000107593), PKD2 (ENSG00000118762), PKDREJ (ENSG00000130943), PKD1L2 (ENSG00000166473), LOXHD1 (ENSG00000167210), DENND5B (ENSG00000170456), DENND5A (ENSG00000184014), PKD1L3 (ENSG00000277481)

Protein

Protein identifiers

Polycystin-1-like protein 1 — Q8TDX9 (reviewed: Q8TDX9)

Alternative names: PC1-like 1 protein, Polycystic kidney disease protein 1-like 1

All UniProt accessions (6): A0A3B3IRH7, A0A8I5KS31, A0A8I5KWV8, A0A8I5QKU1, Q8TDX9, H7C083

UniProt curated annotations — full annotation on UniProt →

Function. Component of a calcium-permeant ion channel formed by PKD1L2 and PKD1L1 in primary cilia, where it controls cilium calcium concentration, without affecting cytoplasmic calcium concentration, and regulates sonic hedgehog/SHH signaling and GLI2 transcription. The PKD1L1:PKD2L1 channel complex is mechanosensitive only at high pressures and is highly temperature sensitive. Also involved in left/right axis specification downstream of nodal flow by forming a complex with PKD2 in cilia to facilitate flow detection in left/right patterning. May function as a G-protein-coupled receptor.

Subunit / interactions. Heterodimer. Interacts with PKD2 to form a calcium channel. Interacts with PKD2L1; to form ciliary calcium channel. May interact with GNA12, GNAS, GNAI1 and GNAI2.

Subcellular location. Cell projection. Cilium membrane.

Tissue specificity. Detected in testis and in fetal and adult heart.

Disease relevance. Heterotaxy, visceral, 8, autosomal (HTX8) [MIM:617205] A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. Visceral heterotaxy or situs ambiguus results in randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another. It can be associated with a variety of congenital defects including cardiac malformations. HTX8 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry. Defects in PKD1L1 may be involved in autosomal recessive congenital chylothorax, a disorder belonging to the congenital lymphatic anomaly spectrum. Congenital chylothorax is characterized by antenatal chyle accumulation in the pleural cavity resulting in fetal lung compression, restricted venous blood flow to the heart and fetal hydrops. Frequently, affected fetuses die intrauterine or shortly after birth. In surviving infants, loss of chyle-soluble fluid leads to malnutrition, thrombophilia, and immunodeficiency.

Similarity. Belongs to the polycystin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TDX9-1	1	yes
Q8TDX9-2	2

RefSeq proteins (1): NP_612152* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000601	PKD_dom	Domain
IPR001024	PLAT/LH2_dom	Domain
IPR002859	PKD/REJ-like	Domain
IPR013122	PKD1_2_channel	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR014010	REJ_dom	Domain
IPR022409	PKD/Chitinase_dom	Domain
IPR035986	PKD_dom_sf	Homologous_superfamily
IPR036392	PLAT/LH2_dom_sf	Homologous_superfamily
IPR042060	PLAT_polycystin1	Domain
IPR046791	Polycystin_dom	Domain
IPR057244	GAIN_B	Domain

Pfam: PF00801, PF01477, PF02010, PF08016, PF20519

UniProt features (73 total): glycosylation site 20, sequence variant 15, topological domain 12, transmembrane region 11, domain 5, region of interest 4, compositionally biased region 2, splice variant 2, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for Q8TDX9 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

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

Disulfide bonds (1): 1691–1717

Glycosylation sites (20): 8, 295, 338, 376, 447, 482, 514, 605, 657, 751, 875, 926, 937, 1233, 1301, 1306, 1572, 1681, 1716, 2426

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 92 (showing top): GOBP_AXIS_SPECIFICATION, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_SPECIFICATION_OF_SYMMETRY, GOBP_CELL_CELL_ADHESION, GOBP_DETECTION_OF_MECHANICAL_STIMULUS, MODULE_205, GOBP_LEFT_RIGHT_AXIS_SPECIFICATION, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, GOBP_DETECTION_OF_ABIOTIC_STIMULUS, GOBP_DETECTION_OF_STIMULUS, GOBP_CALCIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_RESPONSE_TO_MECHANICAL_STIMULUS, GOCC_CELL_PROJECTION_MEMBRANE, GOCC_CATION_CHANNEL_COMPLEX

GO Biological Process (8): detection of nodal flow (GO:0003127), detection of mechanical stimulus (GO:0050982), left/right axis specification (GO:0070986), cell-cell adhesion (GO:0098609), monoatomic ion transport (GO:0006811), calcium ion transport (GO:0006816), monoatomic ion transmembrane transport (GO:0034220), calcium ion transmembrane transport (GO:0070588)

GO Molecular Function (2): calcium channel activity (GO:0005262), protein binding (GO:0005515)

GO Cellular Component (7): cilium (GO:0005929), membrane (GO:0016020), calcium channel complex (GO:0034704), ciliary membrane (GO:0060170), non-motile cilium (GO:0097730), plasma membrane (GO:0005886), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cilium	2
determination of left/right symmetry	1
cellular response to endogenous stimulus	1
detection of external stimulus	1
detection of abiotic stimulus	1
response to mechanical stimulus	1
axis specification	1
left/right pattern formation	1
cell adhesion	1
transport	1
metal ion transport	1
monoatomic ion transport	1
transmembrane transport	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
monoatomic cation channel activity	1
calcium ion transmembrane transporter activity	1
binding	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cation channel complex	1
cell projection membrane	1
bounding membrane of organelle	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

560 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PKD1L1	PKD2L1	Q9P0L9	984
PKD1L1	PRKD1	Q15139	730
PKD1L1	PLAT	P00750	609
PKD1L1	GNA12	Q03113	606
PKD1L1	PKD2L2	Q9NZM6	587
PKD1L1	GNAI2	P04899	586
PKD1L1	CFC1	P0CG37	582
PKD1L1	DAND5	Q8N907	581
PKD1L1	GNAI1	P04898	544
PKD1L1	RHBDD2	Q6NTF9	513
PKD1L1	CFAP53	Q96M91	509
PKD1L1	MMP21	Q8N119	493
PKD1L1	DPCD	Q9BVM2	461
PKD1L1	ZIC3	O60481	446
PKD1L1	SCNN1D	P51172	437

IntAct

2 interactions, top by confidence:

A	B	Type	Score
TEX101	NDUFA4	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): PKD1L1 (Biochemical Activity), PKD1L1 (Proximity Label-MS), PKD1L1 (Proximity Label-MS), PKD1L1 (Affinity Capture-MS), PKD1L1 (Affinity Capture-RNA), PKD1L1 (Affinity Capture-MS), PKD1L1 (Affinity Capture-MS), STX12 (Cross-Linking-MS (XL-MS)), PKD1L1 (Protein-peptide)

ESM2 similar proteins: A0A1B0GV85, A2ALI5, A2APT9, B0BN44, B1ARY8, B6ZI38, O14836, O35188, O55145, O60279, O60667, P07141, P09603, P0C8S2, P28906, P40225, P40226, P42705, P78423, Q06154, Q08DV9, Q13261, Q1ERP8, Q28270, Q2TB54, Q3UY90, Q4V9H3, Q4W8E7, Q5F267, Q5R770, Q60819, Q64314, Q6PAL1, Q6PCP7, Q6UXB8, Q80XI1, Q8BLK9, Q8CAE9, Q8CBC4, Q8JZQ0

Diamond homologs: A2RSQ0, B8UU59, C8YR32, E7FKV8, G3V7Q0, O08852, O16025, P09917, P12527, P48999, P51399, P98161, Q09624, Q2EG98, Q6IQ26, Q6NXD8, Q6PAL8, Q6ZUT9, Q7TN88, Q7Z442, Q7Z443, Q8IVV2, Q8R526, Q8TDX9, Q9NTG1, Q9Z0T6, P39654

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1179 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	26
Likely pathogenic	32
Uncertain significance	546
Likely benign	286
Benign	222

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1027701	NM_138295.5(PKD1L1):c.3601C>T (p.Gln1201Ter)	Pathogenic
1308445	NM_138295.5(PKD1L1):c.7663C>T (p.Arg2555Ter)	Pathogenic
1676821	NM_138295.5(PKD1L1):c.52C>T (p.Gln18Ter)	Pathogenic
1676822	NM_138295.5(PKD1L1):c.411dup (p.Pro138fs)	Pathogenic
1686969	NM_138295.5(PKD1L1):c.8005C>T (p.Arg2669Ter)	Pathogenic
1995733	NM_138295.5(PKD1L1):c.7238del (p.Gly2413fs)	Pathogenic
2065301	NM_138295.5(PKD1L1):c.7937C>G (p.Ser2646Ter)	Pathogenic
2066496	NM_138295.5(PKD1L1):c.8103C>A (p.Cys2701Ter)	Pathogenic
2071911	NM_138295.5(PKD1L1):c.1079T>G (p.Leu360Ter)	Pathogenic
2073168	NM_138295.5(PKD1L1):c.5322del (p.Asp1775fs)	Pathogenic
2080826	NM_138295.5(PKD1L1):c.704G>A (p.Trp235Ter)	Pathogenic
2141863	NM_138295.5(PKD1L1):c.6500G>A (p.Trp2167Ter)	Pathogenic
2197148	NM_138295.5(PKD1L1):c.1071dup (p.His358fs)	Pathogenic
2501763	NM_138295.5(PKD1L1):c.4039C>T (p.Arg1347Ter)	Pathogenic
2501764	NM_138295.5(PKD1L1):c.4798_4799del (p.Gln1600fs)	Pathogenic
2501765	NM_138295.5(PKD1L1):c.1387C>T (p.Gln463Ter)	Pathogenic
2984918	NM_138295.5(PKD1L1):c.2740_2741del (p.Leu914fs)	Pathogenic
3032981	NM_138295.5(PKD1L1):c.6587G>A (p.Trp2196Ter)	Pathogenic
3046698	NM_138295.5(PKD1L1):c.1279G>T (p.Glu427Ter)	Pathogenic
3075706	NM_138295.5(PKD1L1):c.8096_8105del (p.Lys2699fs)	Pathogenic
3336448	NM_138295.5(PKD1L1):c.3011del (p.Ala1004fs)	Pathogenic
3342551	NM_138295.5(PKD1L1):c.427del (p.Ala143fs)	Pathogenic
4702067	NM_138295.5(PKD1L1):c.5813dup (p.Trp1939fs)	Pathogenic
4717006	NM_138295.5(PKD1L1):c.7316del (p.Glu2439fs)	Pathogenic
4820106	NM_138295.5(PKD1L1):c.6618del (p.Glu2207fs)	Pathogenic
873155	NM_138295.5(PKD1L1):c.160+1G>A	Pathogenic
1065357	NM_138295.5(PKD1L1):c.5404_5405dup (p.Asp1803fs)	Likely pathogenic
1299502	NM_138295.5(PKD1L1):c.4938T>G (p.Tyr1646Ter)	Likely pathogenic
1324916	NM_138295.5(PKD1L1):c.5086_5087del (p.Lys1696fs)	Likely pathogenic
1334059	NM_138295.5(PKD1L1):c.6396G>A (p.Trp2132Ter)	Likely pathogenic

SpliceAI

9024 predictions. Top by Δscore:

Variant	Effect	Δscore
7:47792621:TCTTA:T	donor_loss	1.0000
7:47792622:CTTAC:C	donor_loss	1.0000
7:47792623:TTACC:T	donor_loss	1.0000
7:47792624:TA:T	donor_loss	1.0000
7:47792625:A:AC	donor_gain	1.0000
7:47792625:A:AG	donor_loss	1.0000
7:47792626:C:CC	donor_gain	1.0000
7:47792626:CCT:C	donor_gain	1.0000
7:47792793:TAATT:T	acceptor_gain	1.0000
7:47792794:AATT:A	acceptor_gain	1.0000
7:47792795:ATT:A	acceptor_gain	1.0000
7:47792796:TT:T	acceptor_gain	1.0000
7:47792797:TCTG:T	acceptor_loss	1.0000
7:47792798:C:CA	acceptor_loss	1.0000
7:47792798:C:CC	acceptor_gain	1.0000
7:47792799:T:C	acceptor_loss	1.0000
7:47809468:GCTAC:G	donor_loss	1.0000
7:47809469:CTACC:C	donor_loss	1.0000
7:47809470:TACC:T	donor_loss	1.0000
7:47809471:A:C	donor_loss	1.0000
7:47809472:C:A	donor_loss	1.0000
7:47809474:T:TA	donor_gain	1.0000
7:47809484:T:TA	donor_gain	1.0000
7:47809574:CCAG:C	acceptor_gain	1.0000
7:47809575:CAG:C	acceptor_gain	1.0000
7:47809575:CAGC:C	acceptor_gain	1.0000
7:47809576:AGC:A	acceptor_loss	1.0000
7:47809577:GC:G	acceptor_loss	1.0000
7:47809578:C:CC	acceptor_gain	1.0000
7:47809579:T:A	acceptor_loss	1.0000

AlphaMissense

18640 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:47890754:C:A	W821C	0.995
7:47890754:C:G	W821C	0.995
7:47898110:A:G	W717R	0.992
7:47898110:A:T	W717R	0.992
7:47888033:C:A	W931C	0.991
7:47888033:C:G	W931C	0.991
7:47888035:A:G	W931R	0.988
7:47888035:A:T	W931R	0.988
7:47898108:C:A	W717C	0.986
7:47898108:C:G	W717C	0.986
7:47840469:A:C	F1848L	0.984
7:47840469:A:T	F1848L	0.984
7:47840471:A:G	F1848L	0.984
7:47877516:G:C	F1212L	0.984
7:47877516:G:T	F1212L	0.984
7:47877518:A:G	F1212L	0.984
7:47905230:A:G	W540R	0.983
7:47905230:A:T	W540R	0.983
7:47840470:A:G	F1848S	0.981
7:47890756:A:G	W821R	0.981
7:47890756:A:T	W821R	0.981
7:47904437:C:A	W624C	0.981
7:47904437:C:G	W624C	0.981
7:47902475:A:C	N656K	0.980
7:47902475:A:T	N656K	0.980
7:47857659:G:C	S1512R	0.979
7:47857659:G:T	S1512R	0.979
7:47857661:T:G	S1512R	0.979
7:47877605:C:G	A1183P	0.979
7:47893985:A:C	S782R	0.979

dbSNP variants (sampled 300 via entrez): RS1000045553 (7:47872080 T>C), RS1000047970 (7:47806267 G>A), RS1000078762 (7:47806025 G>A,C,T), RS1000081453 (7:47794211 G>T), RS1000113253 (7:47935681 T>G), RS1000120585 (7:47847908 A>G), RS1000127817 (7:47783629 C>A,G), RS1000187133 (7:47899829 GC>G), RS1000190122 (7:47946773 G>A), RS1000195864 (7:47930858 G>A), RS1000205364 (7:47823969 A>T), RS1000211413 (7:47812728 C>A,T), RS1000217859 (7:47864977 C>A,T), RS1000230888 (7:47778331 G>A,T), RS1000238219 (7:47860800 C>G)

Disease associations

OMIM: gene MIM:609721 | disease phenotypes: MIM:617205, MIM:603523, MIM:209850, MIM:306955

GenCC curated gene-disease

Disease	Classification	Inheritance
heterotaxy, visceral, 8, autosomal	Definitive	Autosomal recessive
situs inversus	Supportive	Autosomal dominant

Mondo (5): heterotaxy, visceral, 8, autosomal (MONDO:0014967), congenital chylothorax (MONDO:0011331), situs inversus (MONDO:0010029), autism (MONDO:0005260), visceral heterotaxy (MONDO:0018677)

Orphanet (4): Situs ambiguus (Orphanet:157769), Congenital chylothorax (Orphanet:264688), Situs inversus totalis (Orphanet:101063), Visceral heterotaxy (Orphanet:450)

HPO phenotypes

14 total (16 of 14 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001629	Ventricular septal defect
HP:0001651	Dextrocardia
HP:0001719	Double outlet right ventricle
HP:0003363	Abdominal situs inversus
HP:0003577	Congenital onset
HP:0004383	Hypoplastic left ventricle
HP:0004935	Pulmonary artery atresia
HP:0011538	Atrial situs inversus
HP:0011539	Atrial situs ambiguous
HP:0011540	Levotransposition of the great arteries
HP:0011579	Unbalanced atrioventricular canal defect
HP:0012020	Right aortic arch
HP:0031834	Aortopulmonary collateral arteries
HP:0001696	Situs inversus totalis
HP:0000717	Autism

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001623_6	Hepatitis C induced liver fibrosis	3.000000e-06
GCST002696_12	Anxiety disorder	7.000000e-06
GCST003805_3	Diastolic blood pressure response to hydrochlorothiazide in hypertension	3.000000e-06
GCST005050_3	Obstructive sleep apnea during REM sleep (apnea hypopnea index)	8.000000e-07
GCST007492_4	Waist-to-hip ratio adjusted for BMI (additive genetic model)	4.000000e-06
GCST007494_6	Waist-to-hip ratio adjusted for BMI (additive genetic model)	1.000000e-06
GCST010002_250	Refractive error	1.000000e-11
GCST010817_4	Gut microbiota alpha diversity (Shannon index)	1.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006945	diastolic blood pressure change measurement
EFO:0008455	sleep apnea measurement during REM sleep
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D012857	Situs Inversus	C16.131.810
C535461	Chylothorax, congenital (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation, increases mutagenesis	3
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
methyleugenol	decreases expression	1
bisphenol A	increases methylation	1
sodium arsenite	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
maleic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
licochalcone B	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Fulvestrant	increases methylation	1
Acetaminophen	decreases expression	1
Doxorubicin	decreases expression	1
Endosulfan	increases expression	1
Methapyrilene	decreases methylation	1
Tobacco Smoke Pollution	increases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1584	NCI-H727	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms