KIAA0319

Summary

KIAA0319 (HGNC:21580) is a protein-coding gene on chromosome 6p22.3, encoding Dyslexia-associated protein KIAA0319 (Q5VV43). Involved in neuronal migration during development of the cerebral neocortex.

This gene encodes a transmembrane protein that contains a large extracellular domain with multiple polycystic kidney disease (PKD) domains. The encoded protein may play a role in the development of the cerebral cortex by regulating neuronal migration and cell adhesion. Single nucleotide polymorphisms in this gene are associated with dyslexia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 9856 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 198 total
• MANE Select transcript: NM_014809

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21580
Approved symbol	KIAA0319
Name	KIAA0319
Location	6p22.3
Locus type	gene with protein product
Status	Approved
Aliases	NMIG
Ensembl gene	ENSG00000137261
Ensembl biotype	protein_coding
OMIM	609269
Entrez	9856

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000378214, ENST00000430948, ENST00000535378, ENST00000537886, ENST00000616673, ENST00000901508, ENST00000901509, ENST00000901510, ENST00000937457, ENST00000964874

RefSeq mRNA: 14 — MANE Select: NM_014809 NM_001168374, NM_001168375, NM_001168376, NM_001168377, NM_001252328, NM_001350403, NM_001350404, NM_001350405, NM_001350406, NM_001350407, NM_001350408, NM_001350409, NM_001350410, NM_014809

CCDS: CCDS34348, CCDS54969, CCDS54970, CCDS54971, CCDS75409

Canonical transcript exons

ENST00000378214 — 21 exons

Exon	Start	End
ENSE00000928804	24551434	24551525
ENSE00000928805	24554541	24554631
ENSE00000928806	24556607	24556729
ENSE00000928807	24559013	24559155
ENSE00000928808	24563359	24563518
ENSE00000928809	24564202	24564340
ENSE00000928810	24566597	24566748
ENSE00000928811	24568781	24568929
ENSE00000928812	24569903	24570035
ENSE00000928815	24578110	24578242
ENSE00000928816	24579858	24579950
ENSE00000928817	24580926	24581013
ENSE00000928818	24582249	24582346
ENSE00000928819	24583604	24583702
ENSE00000928820	24588593	24588785
ENSE00001476678	24572575	24572698
ENSE00001476680	24576368	24576596
ENSE00001867942	24544107	24547343
ENSE00003486556	24601049	24601208
ENSE00003641749	24595873	24596618
ENSE00003841833	24645736	24646191

Expression profiles

Bgee: expression breadth ubiquitous, 149 present calls, max score 93.11.

FANTOM5 (CAGE): breadth broad, TPM avg 1.8098 / max 157.8898, expressed in 313 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72189	1.3743	266
72190	0.3644	132
72188	0.0712	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	93.11	gold quality
middle temporal gyrus	UBERON:0002771	92.08	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.86	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.05	gold quality
primary visual cortex	UBERON:0002436	84.81	gold quality
endothelial cell	CL:0000115	83.47	gold quality
entorhinal cortex	UBERON:0002728	82.63	gold quality
Brodmann (1909) area 9	UBERON:0013540	82.49	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.43	gold quality
superior frontal gyrus	UBERON:0002661	82.38	gold quality
prefrontal cortex	UBERON:0000451	82.04	gold quality
lateral nuclear group of thalamus	UBERON:0002736	82.03	gold quality
cingulate cortex	UBERON:0003027	81.65	gold quality
neocortex	UBERON:0001950	81.60	gold quality
anterior cingulate cortex	UBERON:0009835	81.52	gold quality
frontal cortex	UBERON:0001870	81.31	gold quality
occipital lobe	UBERON:0002021	81.18	gold quality
right frontal lobe	UBERON:0002810	81.10	gold quality
cerebral cortex	UBERON:0000956	81.04	gold quality
cerebellar vermis	UBERON:0004720	80.52	gold quality
Brodmann (1909) area 10	UBERON:0013541	80.31	gold quality
nucleus accumbens	UBERON:0001882	80.02	gold quality
telencephalon	UBERON:0001893	79.99	gold quality
caudate nucleus	UBERON:0001873	79.86	gold quality
cerebellar cortex	UBERON:0002129	79.60	gold quality
cerebellar hemisphere	UBERON:0002245	79.57	gold quality
temporal lobe	UBERON:0001871	79.51	gold quality
postcentral gyrus	UBERON:0002581	79.37	gold quality
cerebellum	UBERON:0002037	79.31	gold quality
right hemisphere of cerebellum	UBERON:0014890	78.83	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	58.08
E-HCAD-25	yes	7.79
E-ANND-3	yes	5.82
E-GEOD-83139	yes	4.02

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

106 targeting KIAA0319, 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-1277-5P	100.00	73.95	5056
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-548AC	99.84	70.77	4351

Literature-anchored findings (GeneRIF, showing 40)

• Strong evidence that KIAA0319 on chromosome 6p is a susceptibility gene for developmental dyslexia. (PMID:15717286)
• The risk haplotype on chromosome 6p22.2 down-regulates the KIAA0319 gene which is required for neuronal migration during the formation of the cerebral neocortex. (PMID:16600991)
• a multilocus effect in or near KIAA0319 may influence variation in reading ability. (PMID:17597587)
• widely expressed in adult brain; alternative splicing variants are detected (PMID:17846832)
• results suggest that KIAA0319 could be involved not only in cell-cell interactions, but also in signalling (PMID:18063668)
• we found a nominally significant association for the quantitative dimension “word reading” and KIAA0319 genotype (PMID:18810304)
• KIAA0319 protein is associated with dyslexia. (PMID:18829873)
• identified seven single-nucleotide polymorphisms on the risk haplotype immediately upstream of KIAA0319 and determined that three of these are strongly associated with multiple reading-related traits (PMID:19325871)
• The dyslexia-associated protein KIAA0319 interacts with adaptor protein 2 and follows the classical clathrin-mediated endocytosis pathway. (PMID:19419997)
• acetylated H3 histones in KIAA0319 have a role in reading disabilities (PMID:19588467)
• The results provide additional supportive evidence linking candidate dyslexia susceptibility genes to migrational disturbances during brain development, and extends the role of Kiaa0319 to include growth and differentiation of dendrites. (PMID:19679544)
• KIAA0319 not only has a direct role in neuronal migration but may also have additional signaling functions. (PMID:20943657)
• We identified four rare variants that were significantly associated with the late MMN component. (PMID:21104116)
• At this point, there is no statistical evidence of association between the allelic variation in the three candidate genes and DD in our sample. (PMID:21203818)
• These results support previous studies indicating the 5’ region of the KIAA0319 gene as the location of risk alleles contributing to RD. (PMID:21207242)
• We provide further support for the role of KIAA0319 and DCDC2 in contributing to reading abilities (PMID:21457949)
• Association study of a functional genetic variant in KIAA0319 in German dyslexics. (PMID:21934641)
• The results of this study confirmed that both FOXP2 and KIAA0319/TTRAP/THEM2 genes play an important role in human language development, but probably through different cerebral pathways. (PMID:22262880)
• The Kiaa0319 plays a role in neuronal migration during embryonic development, and that early interference with this gene results in an array of behavioral deficits including impairments in rapid auditory processing and simple spatial learning. (PMID:22326444)
• Mutations in cilia co-expressed DCDC2, DYX1C1 and KIAA0319 genes are associated with a cognitive neurological disorder, dyslexia. (PMID:22558177)
• The results of this study found that KIAA0319 gene contained polymorphisms that were significantly associated with white matter volume in the left temporo-parietal region and that white matter volume influenced reading ability. (PMID:22683091)
• results suggested that the 931C > T variant in KIAA0319, but not the -3G > A in DYX1C1, was significantly associated with the risk of dyslexia (PMID:23065966)
• This study demonstrated the association of developmental dyslexia with rs4504469 of KIAA0319 and not with any single-nucleotide polymorphisms of DCDC2. (PMID:23677054)
• These results indicate that KIAA0319L is the fourth of four candidate dyslexia susceptibility genes that is involved in neuronal migration, which supports the association of abnormal neuronal migration with developmental dyslexia. (PMID:23831424)
• KIAA0319 and ROBO1 genes, and developmental dyslexia (DD), related neuropsychological phenotypes and comorbid language and mathematical (dis)abilities in a large cohort of 493 Italian nuclear families ascertained through a proband with a diagnosis of DD. (PMID:24430574)
• our findings suggest that KIAA0319 is associated with a reading-related cognitive skill (PMID:25015435)
• the association of DCDC2 and KIAA0319 with Developmental dyslexia in Chinese population should be further validated (PMID:25230923)
• Markers in DYX2 genes KIAA0319 and FAM65B were associated with cortical thickness in the left developing orbitofrontal region and global fractional anisotropy, respectively. KIAA0319 and ACOT13 were suggestively associated with overall fractional anisotropy and left pars opercularis cortical thickness, respectively. (PMID:25953057)
• This study indicated that genetic polymorphisms of KIAA0319 are associated with an increased risk of DD in the Uyghur population. (PMID:27098879)
• The study corroborates the importance of rs2038137-KIAA0319, and rs6935076-KIAA0319 in the aetiology of dyslexia. The relevance of rs2038137-KIAA0319, and rs6935076-KIAA0319 was further supported by the meta-analysis. (PMID:27312598)
• a meta-analysis of association studies involving KIAA0319 polymorphisms and Developmental Dyslexia risk, is reported. (PMID:27464509)
• The KIAA0319 gene is associated with both reading ability and general cognition, but in different ways. The effect on IQ appears to occur earlier in development and is transient, whereas the effect of reading ability occurs later and is moderated by antenatal maternal stress. (PMID:27465261)
• Two SNPs in the KIAA0319 gene were nominally associated with rapid naming, and these associations were stable across different ages in longitudinal data set from the Dutch Dyslexia Program. (PMID:28074887)
• Study establishes KIAA0319 as a novel player in axon growth and regeneration with the ability to repress the intrinsic growth potential of axons; describes a novel regulatory mechanism operating during peripheral nervous system and central nervous system axon growth, and offers novel targets for the development of effective therapies to promote axon regeneration (PMID:28334068)
• Missense variant in DYX2 gene is associated with reading disability. (PMID:28866788)
• These findings suggest that DNA methylation patterns in the KIAA0319 promoter region might be associated with cognitive control processes that are necessary to perform well in the forced-attention conditions. (PMID:28958754)
• By suggesting the presence of common biological processes underlying reading (dis)ability, these findings represent initial support for a generalist effect of the non-additive interdependence between READ1 and the KIAA0319 risk haplotype and can help in clinically assessing the individual risk for Developmental dyslexia. (PMID:29066855)
• Residues in strands B and E, and the BC loop of AAVR PKD2 interact directly with the AAV2 capsid. (PMID:30742069)
• Results indicate that the polymorphisms rs4504469, rs2038137, rs2179515, rs3212236, rs6935076, rs9461045, rs2143340 and rs761100 have no association between the polymorphisms and dyslexia risk [Meta-analysis]. (PMID:31204720)
• KIAA0319 influences cilia length, cell migration and mechanical cell-substrate interaction. (PMID:35031635)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	kiaa0319	ENSDARG00000103001
mus_musculus	D130043K22Rik	ENSMUSG00000006711
rattus_norvegicus	Kiaa0319	ENSRNOG00000018141
drosophila_melanogaster	CG7565	FBGN0035833
caenorhabditis_elegans		WBGENE00010792
caenorhabditis_elegans		WBGENE00015355
caenorhabditis_elegans		WBGENE00021939

Paralogs (13): TFPI (ENSG00000003436), EPPIN (ENSG00000101448), TFPI2 (ENSG00000105825), AMBP (ENSG00000106927), LRP11 (ENSG00000120256), WFIKKN1 (ENSG00000127578), KIAA0319L (ENSG00000142687), SPINT4 (ENSG00000149651), WFDC8 (ENSG00000158901), SPINT1 (ENSG00000166145), SPINT2 (ENSG00000167642), WFIKKN2 (ENSG00000173714), WFDC6 (ENSG00000243543)

Protein

Protein identifiers

Dyslexia-associated protein KIAA0319 — Q5VV43 (reviewed: Q5VV43)

All UniProt accessions (2): Q5VV43, A0A087X0U9

UniProt curated annotations — full annotation on UniProt →

Function. Involved in neuronal migration during development of the cerebral neocortex. May function in a cell autonomous and a non-cell autonomous manner and play a role in appropriate adhesion between migrating neurons and radial glial fibers. May also regulate growth and differentiation of dendrites.

Subunit / interactions. Homodimer. Interacts with AP2M1; required for clathrin-mediated endocytosis.

Subcellular location. Cell membrane. Early endosome membrane.

Tissue specificity. Detected in adult brain cortex and fetal frontal lobe (at protein level). Highly expressed in brain cortex, putamen, amygdala, hippocampus and cerebellum.

Post-translational modifications. N-glycosylated. O-glycosylated. Shedding of the extracellular domain and intramembrane cleavage produce several proteolytic products. The intramembrane cleavage releases a soluble cytoplasmic polypeptide that translocates to the nucleolus.

Disease relevance. Dyslexia 2 (DYX2) [MIM:600202] A relatively common, complex cognitive disorder characterized by an impairment of reading performance despite adequate motivational, educational and intellectual opportunities. It is a multifactorial trait, with evidence for familial clustering and heritability. Disease susceptibility may be associated with variants affecting the gene represented in this entry.

Isoforms (4)

UniProt ID	Names	Canonical?
Q5VV43-1	1, A	yes
Q5VV43-2	2
Q5VV43-3	3
Q5VV43-4	4

RefSeq proteins (14): NP_001161846, NP_001161847, NP_001161848, NP_001161849, NP_001239257, NP_001337332, NP_001337333, NP_001337334, NP_001337335, NP_001337336, NP_001337337, NP_001337338, NP_001337339, NP_055624* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000601	PKD_dom	Domain
IPR003961	FN3_dom	Domain
IPR011106	MANSC_N	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR013980	MANSC_dom	Domain
IPR022409	PKD/Chitinase_dom	Domain
IPR029865	KIAA0319-like	Family
IPR035986	PKD_dom_sf	Homologous_superfamily
IPR056502	KIAA0319-like_C	Domain

Pfam: PF22352, PF23597, PF23620

UniProt features (53 total): glycosylation site 10, strand 10, sequence variant 7, domain 6, sequence conflict 4, region of interest 3, compositionally biased region 3, splice variant 3, topological domain 2, signal peptide 1, chain 1, short sequence motif 1, transmembrane region 1, mutagenesis site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2E7M	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VV43-F1	70.91	0.28

Functional residue map

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

Glycosylation sites (10): 196, 219, 262, 394, 421, 498, 513, 536, 551, 733

Mutagenesis-validated functional residues (1):

Position	Phenotype
995	loss of interaction with ap2m1 and impaired endocytosis.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport

MSigDB gene sets: 171 (showing top): GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_DENDRITE_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_NEGATIVE_REGULATION_OF_AXON_EXTENSION, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_GROWTH, GOBP_REGENERATION, GOBP_NEUROGENESIS, GOBP_RESPONSE_TO_AXON_INJURY, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_NEGATIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_GROWTH

GO Biological Process (12): neuron migration (GO:0001764), sensory perception of sound (GO:0007605), thalamus development (GO:0021794), central nervous system neuron development (GO:0021954), negative regulation of axon extension (GO:0030517), multicellular organismal response to stress (GO:0033555), vocal learning (GO:0042297), negative regulation of axon extension involved in regeneration (GO:0048692), positive regulation of SMAD protein signal transduction (GO:0060391), negative regulation of dendrite development (GO:2000171), nervous system development (GO:0007399), response to auditory stimulus (GO:0010996)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (7): early endosome (GO:0005769), plasma membrane (GO:0005886), clathrin-coated endocytic vesicle membrane (GO:0030669), cytoplasmic vesicle (GO:0031410), early endosome membrane (GO:0031901), endosome (GO:0005768), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Clathrin-mediated endocytosis	1
Membrane Trafficking	1
Vesicle-mediated transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell migration	1
generation of neurons	1
sensory perception of mechanical stimulus	1
diencephalon development	1
anatomical structure development	1
central nervous system neuron differentiation	1
neuron development	1
negative regulation of cell growth	1
regulation of axon extension	1
negative regulation of developmental growth	1
axon extension	1
negative regulation of axonogenesis	1
response to stress	1
multicellular organismal process	1
auditory behavior	1
imitative learning	1
learned vocalization behavior or vocal learning	1
negative regulation of axon extension	1
axon extension involved in regeneration	1
negative regulation of sprouting of injured axon	1
regulation of SMAD protein signal transduction	1
SMAD protein signal transduction	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
positive regulation of intracellular signal transduction	1
negative regulation of neuron projection development	1
dendrite development	1
regulation of dendrite development	1
negative regulation of developmental process	1
system development	1
response to mechanical stimulus	1
binding	1
endosome	1
membrane	1
cell periphery	1
clathrin-coated vesicle membrane	1
endocytic vesicle membrane	1
clathrin-coated endocytic vesicle	1
cytoplasm	1
intracellular vesicle	1
early endosome	1

Protein interactions and networks

STRING

964 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KIAA0319	DCDC2	Q9UHG0	986
KIAA0319	DNAAF4	Q8WXU2	972
KIAA0319	ACOT13	Q9NPJ3	945
KIAA0319	TDP2	O95551	930
KIAA0319	GCFC2	P16383	780
KIAA0319	ROBO1	Q9Y6N7	773
KIAA0319	MRPL19	P49406	727
KIAA0319	ATP2C2	O75185	701
KIAA0319	CMIP	Q8IY22	684
KIAA0319	KAAG1	Q9UBP8	670
KIAA0319	DOCK3	Q8IZD9	669
KIAA0319	CNTNAP2	Q9UHC6	667
KIAA0319	FOXP2	O15409	662
KIAA0319	DCX	O43602	639
KIAA0319	NRSN1	Q8IZ57	582

IntAct

6 interactions, top by confidence:

A	B	Type	Score
APP	KIAA0319	psi-mi:“MI:0915”(physical association)	0.370
KIAA0319	FEM1B	psi-mi:“MI:0915”(physical association)	0.370
KIAA0319	SH2B1	psi-mi:“MI:0915”(physical association)	0.370
	SHTN1	psi-mi:“MI:0914”(association)	0.350
MYC		psi-mi:“MI:0914”(association)	0.350

BioGRID (5): KIAA0319 (Two-hybrid), KIAA0319 (Affinity Capture-MS), NUP205 (Cross-Linking-MS (XL-MS)), FEM1B (Two-hybrid), SH2B1 (Two-hybrid)

ESM2 similar proteins: A7E2Z9, A8K7I4, B7ZSK1, C6KFA3, P07911, P15396, P17301, P19218, P52787, P53710, Q14CN2, Q16819, Q1WIM2, Q2TU62, Q5T601, Q5VV43, Q5Y4N8, Q61549, Q62469, Q62929, Q66IR0, Q6DJ83, Q6F3F9, Q6PT52, Q6Q473, Q6QMG1, Q6YHK3, Q70VB1, Q862Z3, Q86SQ4, Q8BGZ8, Q8BLQ9, Q8BM96, Q8CJ11, Q8CJ12, Q8IZP9, Q8K4Z6, Q8N3J6, Q8TCW7, Q91X17

Diamond homologs: P0CI71, Q5RFR6, Q5SZV5, Q5VV43, Q86VZ4, Q8CB67, Q8IZA0, Q8K135, Q9X721, P06682, P79755

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	150
Likely benign	19
Benign	11

Top pathogenic / likely-pathogenic (0)

SpliceAI

4480 predictions. Top by Δscore:

Variant	Effect	Δscore
6:24563353:TCCTA:T	donor_loss	1.0000
6:24563354:CCTAC:C	donor_loss	1.0000
6:24563356:TACCT:T	donor_loss	1.0000
6:24563357:ACCTG:A	donor_loss	1.0000
6:24563358:CCTG:C	donor_loss	1.0000
6:24563384:TCTGG:T	donor_gain	1.0000
6:24563515:GGGT:G	acceptor_gain	1.0000
6:24563516:GGT:G	acceptor_gain	1.0000
6:24563517:GT:G	acceptor_gain	1.0000
6:24563518:TC:T	acceptor_loss	1.0000
6:24563519:C:CC	acceptor_gain	1.0000
6:24563519:C:CG	acceptor_loss	1.0000
6:24564197:CTCA:C	donor_loss	1.0000
6:24564198:TCAC:T	donor_loss	1.0000
6:24564199:CA:C	donor_loss	1.0000
6:24564200:A:AC	donor_gain	1.0000
6:24564200:A:C	donor_loss	1.0000
6:24564201:C:A	donor_loss	1.0000
6:24564201:C:CC	donor_gain	1.0000
6:24564201:CCTGG:C	donor_gain	1.0000
6:24564337:CATC:C	acceptor_gain	1.0000
6:24564339:TC:T	acceptor_gain	1.0000
6:24564340:CC:C	acceptor_gain	1.0000
6:24564341:C:CC	acceptor_gain	1.0000
6:24565917:TGG:T	donor_gain	1.0000
6:24568779:AC:A	donor_gain	1.0000
6:24568780:CC:C	donor_gain	1.0000
6:24568780:CCCTT:C	donor_gain	1.0000
6:24568928:CT:C	acceptor_gain	1.0000
6:24568930:C:CC	acceptor_gain	1.0000

AlphaMissense

7020 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:24576412:A:G	W564R	0.997
6:24576412:A:T	W564R	0.997
6:24576443:G:C	S553R	0.996
6:24576443:G:T	S553R	0.996
6:24576445:T:G	S553R	0.996
6:24572637:A:G	L599P	0.995
6:24576410:C:A	W564C	0.995
6:24576410:C:G	W564C	0.995
6:24582326:A:G	W372R	0.993
6:24582326:A:T	W372R	0.993
6:24578238:A:C	S459R	0.992
6:24578238:A:T	S459R	0.992
6:24578240:T:G	S459R	0.992
6:24578205:C:A	W470C	0.991
6:24578205:C:G	W470C	0.991
6:24569914:C:A	W660C	0.989
6:24569914:C:G	W660C	0.989
6:24576594:A:G	L503S	0.989
6:24569947:G:C	S649R	0.988
6:24569947:G:T	S649R	0.988
6:24569949:T:G	S649R	0.988
6:24582324:C:A	W372C	0.988
6:24582324:C:G	W372C	0.988
6:24572583:A:T	V617D	0.987
6:24566629:A:G	W754R	0.985
6:24566629:A:T	W754R	0.985
6:24578207:A:G	W470R	0.984
6:24578207:A:T	W470R	0.984
6:24576459:A:G	L548S	0.983
6:24566609:A:C	S760R	0.982

dbSNP variants (sampled 300 via entrez): RS1000051148 (6:24620350 A>C), RS1000056499 (6:24568107 T>C), RS1000061878 (6:24577290 GC>G), RS1000196054 (6:24633820 T>C,G), RS1000196396 (6:24558174 G>A), RS1000257276 (6:24594889 C>T), RS1000297102 (6:24639076 C>T), RS1000306745 (6:24619210 G>A), RS1000325479 (6:24598895 TA>T,TAA), RS1000325495 (6:24613957 G>A), RS1000356528 (6:24606316 T>C), RS1000358857 (6:24607552 A>G), RS1000360878 (6:24633146 A>G), RS1000377251 (6:24587406 A>G), RS1000395584 (6:24627651 C>T)

Disease associations

OMIM: gene MIM:609269 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000823_1	Radiation response	2.000000e-06
GCST007733_27	Serum uric acid levels	3.000000e-07
GCST008159_5	Waist-to-hip ratio adjusted for BMI	9.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004761	uric acid measurement
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Phenylmercuric Acetate	affects cotreatment, increases expression	2
lasiocarpine	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
sulforaphane	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Troglitazone	increases expression	1
Aldehydes	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Formaldehyde	increases expression	1
Lead	affects expression	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Methapyrilene	increases methylation	1
Pesticides	affects methylation	1
Tobacco Smoke Pollution	affects expression	1
Triclosan	decreases expression	1
Valproic Acid	increases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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