ANKRD27

Summary

ANKRD27 (ankyrin repeat domain 27, HGNC:25310) is a protein-coding gene on chromosome 19q13.11, encoding Ankyrin repeat domain-containing protein 27 (Q96NW4). May be a guanine exchange factor (GEF) for Rab21, Rab32 and Rab38 and regulate endosome dynamics.

Enables guanyl-nucleotide exchange factor activity and small GTPase binding activity. Involved in endocytic recycling and negative regulation of SNARE complex assembly. Acts upstream of or within early endosome to late endosome transport. Located in several cellular components, including cytosol; endosome; and lysosome. Implicated in eosinophilic esophagitis.

Source: NCBI Gene 84079 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 222 total — 1 pathogenic
• MANE Select transcript: NM_032139

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25310
Approved symbol	ANKRD27
Name	ankyrin repeat domain 27
Location	19q13.11
Locus type	gene with protein product
Status	Approved
Aliases	FLJ00040, DKFZp434L0718, VARP
Ensembl gene	ENSG00000105186
Ensembl biotype	protein_coding
OMIM	618957
Entrez	84079

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 25 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000306065, ENST00000586463, ENST00000586693, ENST00000587352, ENST00000587667, ENST00000588700, ENST00000590519, ENST00000591100, ENST00000593232, ENST00000879685, ENST00000879686, ENST00000879687, ENST00000879688, ENST00000879689, ENST00000879690, ENST00000879691, ENST00000879692, ENST00000879693, ENST00000920852, ENST00000920853, ENST00000920854, ENST00000920855, ENST00000920856, ENST00000920857, ENST00000964138, ENST00000964139, ENST00000964140, ENST00000964141

RefSeq mRNA: 1 — MANE Select: NM_032139 NM_032139

CCDS: CCDS32986

Canonical transcript exons

ENST00000306065 — 29 exons

Exon	Start	End
ENSE00000694712	32602015	32602126
ENSE00000694717	32604263	32604424
ENSE00000821613	32605835	32605954
ENSE00000821614	32615658	32615780
ENSE00000821615	32617589	32617633
ENSE00000821617	32619494	32619553
ENSE00000821618	32622422	32622619
ENSE00000821619	32625874	32625966
ENSE00000821622	32628722	32628849
ENSE00000821623	32631402	32631494
ENSE00000821624	32639356	32639488
ENSE00000821626	32642024	32642145
ENSE00001161479	32599972	32600050
ENSE00001161486	32607635	32607832
ENSE00001161503	32619260	32619379
ENSE00001161511	32626712	32626827
ENSE00001220564	32597006	32598378
ENSE00002958563	32675071	32675180
ENSE00003461280	32640307	32640385
ENSE00003478938	32643287	32643352
ENSE00003491746	32643572	32643631
ENSE00003565554	32599704	32599776
ENSE00003664096	32644325	32644479
ENSE00003682874	32643431	32643484
ENSE00003704310	32658914	32659045
ENSE00003707318	32649682	32649792
ENSE00003707893	32646459	32646615
ENSE00003710486	32628083	32628165
ENSE00003785855	32643123	32643199

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 94.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.7766 / max 125.5891, expressed in 1798 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180390	15.7766	1798

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
choroid plexus epithelium	UBERON:0003911	94.70	gold quality
amniotic fluid	UBERON:0000173	94.28	gold quality
upper leg skin	UBERON:0004262	91.87	gold quality
palpebral conjunctiva	UBERON:0001812	91.54	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.99	gold quality
cauda epididymis	UBERON:0004360	89.98	gold quality
seminal vesicle	UBERON:0000998	89.91	gold quality
epithelium of nasopharynx	UBERON:0001951	89.71	gold quality
nasopharynx	UBERON:0001728	89.70	gold quality
lower lobe of lung	UBERON:0008949	89.69	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.47	gold quality
urethra	UBERON:0000057	89.31	gold quality
endothelial cell	CL:0000115	89.21	silver quality
mucosa of sigmoid colon	UBERON:0004993	89.10	gold quality
esophagus squamous epithelium	UBERON:0006920	89.08	gold quality
urinary bladder	UBERON:0001255	88.99	gold quality
colonic mucosa	UBERON:0000317	88.91	gold quality
saphenous vein	UBERON:0007318	88.74	gold quality
blood vessel layer	UBERON:0004797	88.60	gold quality
skin of hip	UBERON:0001554	88.40	gold quality
placenta	UBERON:0001987	88.29	gold quality
trabecular bone tissue	UBERON:0002483	88.10	gold quality
parietal pleura	UBERON:0002400	88.08	gold quality
epithelium of esophagus	UBERON:0001976	88.02	gold quality
tibia	UBERON:0000979	87.98	gold quality
jejunal mucosa	UBERON:0000399	87.78	gold quality
cartilage tissue	UBERON:0002418	87.75	gold quality
adult organism	UBERON:0007023	87.52	gold quality
cerebellar vermis	UBERON:0004720	87.41	gold quality
pleura	UBERON:0000977	87.39	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-112	yes	6.75
E-MTAB-9801	yes	6.64
E-ANND-3	yes	6.40

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

104 targeting ANKRD27, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-4698	99.84	71.41	4303

Literature-anchored findings (GeneRIF, showing 6)

• Varp physically interacts with Rab38, and preferentially binds to the active GTP-bound form of Rab38 both in vitro and in vivo. (PMID:18477474)
• show that TI-VAMP interacts with the Vps9 domain and ankyrin-repeat-containing protein Varp, a guanine nucleotide exchange factor of the small GTPase Rab21, through a specific domain herein called the interacting domain. (PMID:19745841)
• VAMP7-SNARE motif is trapped between Varp and the VAMP7 longin domain, and hence Varp kinetically inhibits the ability of VAMP7 to form SNARE complexes (PMID:23104059)
• Eosinophilic esophagitis was associate with increased expression of ANKRD27. (PMID:25407941)
• VARP regulates endosomal trafficking and and retromer-mediated endosome-to-plasma membrane sorting of transmembrane proteins by binding to rab GTP-Binding Proteins and R-SNARE VAMP7 [review]. (PMID:27103185)
• Mechanism and evolution of the Zn-fingernail required for interaction of VARP with VPS29. (PMID:33024112)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ankrd27	ENSDARG00000089207
mus_musculus	Ankrd27	ENSMUSG00000034867
rattus_norvegicus	Ankrd27	ENSRNOG00000052814

Protein

Protein identifiers

Ankyrin repeat domain-containing protein 27 — Q96NW4 (reviewed: Q96NW4)

Alternative names: VPS9 domain-containing protein

All UniProt accessions (7): Q96NW4, K7EIH4, K7EIN0, K7ELM1, K7ENE0, K7EPM2, V9GYL8

UniProt curated annotations — full annotation on UniProt →

Function. May be a guanine exchange factor (GEF) for Rab21, Rab32 and Rab38 and regulate endosome dynamics. May regulate the participation of VAMP7 in membrane fusion events; in vitro inhibits VAMP7-mediated SNARE complex formation by trapping VAMP7 in a closed, fusogenically inactive conformation. Involved in peripheral melanosomal distribution of TYRP1 in melanocytes; the function, which probably is implicating vesicle-trafficking, includes cooperation with Rab32, Rab38 and VAMP7. Involved in the regulation of neurite growth; the function seems to require its GEF activity, probably towards Rab21, and VAMP7 but not Rab32/38. Proposed to be involved in Golgi sorting of VAMP7 and transport of VAMP7 vesicles to the cell surface; the function seems to implicate kinesin heavy chain isoform 5 proteins, GOLGA4, RAB21 and MACF1. Required for the colocalization of VAMP7 and Rab21, probably on TGN sites. Involved in GLUT1 endosome-to-plasma membrane trafficking; the function is dependent of association with VPS29. Regulates the proper trafficking of melanogenic enzymes TYR, TYRP1 and DCT/TYRP2 to melanosomes in melanocytes.

Subunit / interactions. Interacts with RAB21 (GDP-bound form), VPS29, RAB32 (GTP-bound form), RAB38 (GTP-bound form), VAMP7, KIF5A, KIF5C, GOLGA4. Interacts with low affinity with RAB5. ANKRD27:RAB32 heterodimers can homodimerize to form tetramers. Can interact with RAB38 or RAB32, VPS29 and VAMP7 simultaneously. A decreased interaction with RAB32 seen in the presence of SGSM2.

Subcellular location. Early endosome. Late endosome. Cytoplasmic vesicle membrane. Lysosome. Cell membrane. Melanosome.

RefSeq proteins (1): NP_115515* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR003123	VPS9	Domain
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR037191	VPS9_dom_sf	Homologous_superfamily
IPR051248	UPF0507/Ank_repeat_27	Family

Pfam: PF00023, PF02204, PF12796

UniProt features (69 total): helix 23, mutagenesis site 12, repeat 11, region of interest 8, compositionally biased region 4, modified residue 3, sequence variant 2, strand 2, chain 1, domain 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
4B93	X-RAY DIFFRACTION	2
4CYM	X-RAY DIFFRACTION	2.8
4CZ2	X-RAY DIFFRACTION	2.97
6TL0	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96NW4-F1	68.33	0.12

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 (3): 962, 970, 1023

Mutagenesis-validated functional residues (12):

Position	Phenotype
432	disrupts interaction with vps29; when associated with a-434.
434	disrupts interaction with vps29; when associated with a-432.
509	disrupts interaction with rab32.
513	disrupts interaction with rab32.
546	impairs interaction with rab32.
550	impairs interaction with rab32.
679	disrupts interaction with vamp7.
681	disrupts interaction with vamp7.
684	disrupts interaction with vamp7.
687	disrupts interaction with vamp7.
712	disrupts interaction with vps29; when associated with a-714.
714	disrupts interaction with vps29; when associated with a-712.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport
R-HSA-9007101	Rab regulation of trafficking

MSigDB gene sets: 202 (showing top): GOBP_DENDRITE_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_REGULATION_OF_VESICLE_FUSION, BENPORATH_ES_WITH_H3K27ME3, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_VESICLE_ORGANIZATION, GOBP_REGULATION_OF_DENDRITE_MORPHOGENESIS, GOBP_MEMBRANE_FUSION, GOBP_CELLULAR_PIGMENTATION, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, REACTOME_MEMBRANE_TRAFFICKING, GOMF_GTPASE_BINDING, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS

GO Biological Process (8): positive regulation of neuron projection development (GO:0010976), protein transport (GO:0015031), endocytic recycling (GO:0032456), negative regulation of SNARE complex assembly (GO:0035544), endosome to melanosome transport (GO:0035646), early endosome to late endosome transport (GO:0045022), neuron projection morphogenesis (GO:0048812), positive regulation of dendrite morphogenesis (GO:0050775)

GO Molecular Function (5): SNARE binding (GO:0000149), guanyl-nucleotide exchange factor activity (GO:0005085), GTPase activator activity (GO:0005096), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (14): lysosome (GO:0005764), early endosome (GO:0005769), late endosome (GO:0005770), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), transport vesicle (GO:0030133), cytoplasmic vesicle membrane (GO:0030659), melanosome (GO:0042470), neuron projection (GO:0043005), tubular endosome (GO:0097422), endosome (GO:0005768), endomembrane system (GO:0012505), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Rab regulation of trafficking	1
Vesicle-mediated transport	1
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	3
endosome	3
cytoplasmic vesicle	3
neuron projection development	2
positive regulation of cell projection organization	2
GTPase regulator activity	2
endomembrane system	2
regulation of neuron projection development	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
endosomal transport	1
vesicle-mediated transport to the plasma membrane	1
negative regulation of protein-containing complex assembly	1
negative regulation of vesicle fusion	1
SNARE complex assembly	1
regulation of SNARE complex assembly	1
endosome to pigment granule transport	1
vesicle-mediated transport between endosomal compartments	1
plasma membrane bounded cell projection morphogenesis	1
positive regulation of cell morphogenesis	1
dendrite morphogenesis	1
regulation of dendrite morphogenesis	1
positive regulation of neurogenesis	1
protein binding	1
GTP binding	1
GDP binding	1
GTPase activity	1
enzyme activator activity	1
GTPase binding	1
binding	1
lytic vacuole	1
membrane	1
cell periphery	1
vesicle membrane	1
pigment granule	1
plasma membrane bounded cell projection	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

1789 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANKRD27	RAB32	Q13637	951
ANKRD27	VAMP7	P51809	950
ANKRD27	RAB38	P57729	889
ANKRD27	GOLGA4	Q13439	815
ANKRD27	RAB21	Q9UL25	801
ANKRD27	VPS29	Q9UBQ0	735
ANKRD27	KIF5A	Q12840	658
ANKRD27	VPS35	Q96QK1	631
ANKRD27	RABIF	P47224	621
ANKRD27	YKT6	O15498	606
ANKRD27	RAB3IP	Q96QF0	587
ANKRD27	ENTR1	Q96C92	581
ANKRD27	TBC1D5	Q92609	577
ANKRD27	CAPN14	A8MX76	574
ANKRD27	VPS26A	O75436	560

IntAct

77 interactions, top by confidence:

A	B	Type	Score
VPS35	VPS26A	psi-mi:“MI:0914”(association)	0.980
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
VPS29	VPS26C	psi-mi:“MI:0914”(association)	0.760
VPS29	VPS26B	psi-mi:“MI:0914”(association)	0.730
Vamp7	ANKRD27	psi-mi:“MI:0407”(direct interaction)	0.700
Vamp7	ANKRD27	psi-mi:“MI:0915”(physical association)	0.700
NFKBIA	POLRMT	psi-mi:“MI:0914”(association)	0.670
HIF1AN	GMDS	psi-mi:“MI:0914”(association)	0.640
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
Vamp7	Vti1b	psi-mi:“MI:0914”(association)	0.620
KIF5A	ANKRD27	psi-mi:“MI:0915”(physical association)	0.580
ANKRD27	KIF5A	psi-mi:“MI:0915”(physical association)	0.580
Vamp7	ANKRD27	psi-mi:“MI:0915”(physical association)	0.580
ANKRD27	Vamp7	psi-mi:“MI:0915”(physical association)	0.580

BioGRID (71): ANKRD27 (Affinity Capture-MS), ANKRD27 (Affinity Capture-MS), RAB40A (Two-hybrid), RAB40B (Two-hybrid), RAB40C (Two-hybrid), ANKRD27 (Affinity Capture-MS), ANKRD27 (Affinity Capture-MS), ANKRD27 (Affinity Capture-MS), ANKRD27 (Affinity Capture-MS), ANKRD27 (Affinity Capture-MS), ANKRD27 (Affinity Capture-MS), ANKRD27 (Affinity Capture-MS), ANKRD27 (Affinity Capture-MS), ANKRD27 (Affinity Capture-MS), ANKRD27 (Affinity Capture-MS)

ESM2 similar proteins: A0JPF9, A4D126, A4D7T3, A4QNL8, A5PKL6, B2GUS6, C0IN03, E1BCH6, E1BVR9, F1LW30, F1ND48, P19686, P19687, P33402, P48760, P57075, Q02108, Q07DZ7, Q08C84, Q09M05, Q108U1, Q1L5Z9, Q1LZ50, Q28CZ7, Q32PY6, Q3U3W5, Q3UY23, Q4R3W5, Q4ZHS0, Q5REW9, Q5RG49, Q5RJG7, Q5RL51, Q5S6T3, Q5T8I9, Q6GPJ4, Q6NXP6, Q6P2P2, Q7SXA9, Q8BTK5

Diamond homologs: O18973, O74396, P54787, Q10NQ3, Q5REW9, Q96NW4, Q9JM13, Q9LT31, Q9UJ41, Q9VZ08, Q3UMR0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 68 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
RHO GTPase Effectors	5	7.4×	9e-03
Membrane Trafficking	9	7.2×	6e-04
Vesicle-mediated transport	9	6.8×	6e-04

GO biological processes:

GO term	Partners	Fold	FDR
endocytic recycling	5	23.1×	3e-04
retrograde transport, endosome to Golgi	6	21.3×	6e-05
vesicle-mediated transport	8	13.3×	3e-05
intracellular protein transport	10	11.2×	9e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	165
Likely benign	12
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
153499	GRCh38/hg38 19q12-13.12(chr19:31367353-35417098)x1	Pathogenic

SpliceAI

4472 predictions. Top by Δscore:

Variant	Effect	Δscore
19:32599970:A:AC	donor_gain	1.0000
19:32599971:C:CC	donor_gain	1.0000
19:32600051:C:A	acceptor_loss	1.0000
19:32600051:C:CC	acceptor_gain	1.0000
19:32600052:T:G	acceptor_loss	1.0000
19:32602009:TCTTA:T	donor_loss	1.0000
19:32602010:CTTA:C	donor_loss	1.0000
19:32602011:TTAC:T	donor_loss	1.0000
19:32602012:TA:T	donor_loss	1.0000
19:32602013:A:AC	donor_gain	1.0000
19:32602014:C:CC	donor_gain	1.0000
19:32602014:CA:C	donor_gain	1.0000
19:32602014:CAT:C	donor_gain	1.0000
19:32602014:CATT:C	donor_gain	1.0000
19:32602021:T:A	donor_gain	1.0000
19:32602032:A:C	donor_gain	1.0000
19:32602042:A:AC	donor_gain	1.0000
19:32602042:ACT:A	donor_gain	1.0000
19:32602043:C:CC	donor_gain	1.0000
19:32602043:CTC:C	donor_gain	1.0000
19:32602134:T:C	acceptor_gain	1.0000
19:32602134:T:TC	acceptor_gain	1.0000
19:32604260:TA:T	donor_loss	1.0000
19:32604261:A:AC	donor_gain	1.0000
19:32604262:C:CC	donor_gain	1.0000
19:32604420:CCGTG:C	acceptor_gain	1.0000
19:32604421:CGTG:C	acceptor_gain	1.0000
19:32604421:CGTGC:C	acceptor_gain	1.0000
19:32604422:GTG:G	acceptor_gain	1.0000
19:32604422:GTGC:G	acceptor_loss	1.0000

AlphaMissense

6897 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:32622534:G:T	A572D	0.998
19:32640308:A:G	W328R	0.997
19:32640308:A:T	W328R	0.997
19:32625892:G:C	C537W	0.996
19:32622532:C:G	A573P	0.995
19:32625894:A:G	C537R	0.995
19:32626738:A:G	C504R	0.995
19:32642128:G:T	A267D	0.995
19:32604370:C:G	A850P	0.994
19:32615690:A:G	C715R	0.994
19:32622498:A:G	L584S	0.994
19:32622531:G:T	A573D	0.994
19:32625893:C:T	C537Y	0.994
19:32625896:G:T	A536D	0.994
19:32628091:G:T	A471D	0.994
19:32628092:C:G	A471P	0.994
19:32628094:G:T	A470D	0.994
19:32615689:C:G	C715S	0.993
19:32615690:A:T	C715S	0.993
19:32622528:C:G	R574P	0.993
19:32625959:A:G	L515P	0.993
19:32626736:A:C	C504W	0.993
19:32643439:C:G	A211P	0.993
19:32615674:C:G	C720S	0.992
19:32615675:A:T	C720S	0.992
19:32615684:A:G	C717R	0.992
19:32628103:A:T	L467H	0.992
19:32639403:C:G	A357P	0.992
19:32642116:A:G	L271P	0.992
19:32642124:T:A	K268N	0.992

dbSNP variants (sampled 300 via entrez): RS1000017029 (19:32676132 G>A,T), RS1000056075 (19:32671980 G>A), RS1000106762 (19:32599872 G>A,C), RS1000107241 (19:32635340 T>C), RS1000123534 (19:32633076 T>C), RS1000139464 (19:32600238 C>A), RS1000170718 (19:32653458 G>C), RS1000177778 (19:32616753 T>C), RS1000206634 (19:32630078 A>AT), RS1000218478 (19:32665707 C>T), RS1000259136 (19:32630297 A>G,T), RS1000396562 (19:32660223 G>A,C), RS1000470828 (19:32649410 C>A,G,T), RS1000486858 (19:32659275 T>C,G), RS1000491459 (19:32622681 C>G)

Disease associations

OMIM: gene MIM:618957 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001850_7	Major depressive disorder	7.000000e-07
GCST002697_5	Eosinophilic esophagitis	2.000000e-09
GCST004621_163	Red cell distribution width	2.000000e-12
GCST006585_2673	Blood protein levels	3.000000e-07
GCST006804_184	Red cell distribution width	4.000000e-08
GCST011096_18	Systemic lupus erythematosus	2.000000e-09
GCST90006988_6	Gut microbiota relative abundance (Bacteroides)	7.000000e-06
GCST90011866_21	Systemic lupus erythematosus	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation	1
trichostatin A	affects expression	1
beta-lapachone	increases expression	1
aflatoxin B2	decreases methylation	1
perfluoro-n-nonanoic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Caffeine	affects phosphorylation	1
Carbamazepine	affects expression	1
Cycloheximide	affects cotreatment, increases expression	1
Methyl Methanesulfonate	decreases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	1
Tretinoin	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	increases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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