ABR

Summary

ABR (ABR activator of RhoGEF and GTPase, HGNC:81) is a protein-coding gene on chromosome 17p13.3, encoding Active breakpoint cluster region-related protein (Q12979). Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins.

This gene encodes a protein that is similar to the protein encoded by the breakpoint cluster region gene located on chromosome 22. The protein encoded by this gene contains a GTPase-activating protein domain, a domain found in members of the Rho family of GTP-binding proteins. Functional studies in mice determined that this protein plays a role in vestibular morphogenesis. Alternatively spliced transcript variants have been reported for this gene.

Source: NCBI Gene 29 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 227 total — 53 pathogenic, 16 likely-pathogenic
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_021962

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:81
Approved symbol	ABR
Name	ABR activator of RhoGEF and GTPase
Location	17p13.3
Locus type	gene with protein product
Status	Approved
Aliases	MDB
Ensembl gene	ENSG00000159842
Ensembl biotype	protein_coding
OMIM	600365
Entrez	29

Gene structure

Transcript identifiers

Ensembl transcripts: 39 — 18 protein_coding, 10 retained_intron, 9 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000291107, ENST00000302538, ENST00000536794, ENST00000543210, ENST00000544583, ENST00000570441, ENST00000570525, ENST00000570688, ENST00000571022, ENST00000571120, ENST00000571306, ENST00000571383, ENST00000571543, ENST00000571797, ENST00000571945, ENST00000572152, ENST00000572441, ENST00000572585, ENST00000572650, ENST00000573325, ENST00000573559, ENST00000573667, ENST00000573895, ENST00000574048, ENST00000574139, ENST00000574257, ENST00000574266, ENST00000574437, ENST00000574544, ENST00000574632, ENST00000574875, ENST00000575770, ENST00000575934, ENST00000576668, ENST00000576964, ENST00000577052, ENST00000885050, ENST00000926226, ENST00000967956

RefSeq mRNA: 7 — MANE Select: NM_021962 NM_001092, NM_001159746, NM_001256847, NM_001282149, NM_001322840, NM_001322841, NM_021962

CCDS: CCDS10999, CCDS11000, CCDS54060, CCDS58497, CCDS73936, CCDS92217

Canonical transcript exons

ENST00000302538 — 23 exons

Exon	Start	End
ENSE00001048048	1058745	1058867
ENSE00001128705	1057970	1058045
ENSE00001199233	1067077	1067242
ENSE00001248336	1083520	1083627
ENSE00001868366	1003519	1006169
ENSE00002337964	1091665	1091850
ENSE00002658131	1179667	1179981
ENSE00003479189	1073625	1073677
ENSE00003485214	1012688	1012797
ENSE00003501031	1011846	1011985
ENSE00003515441	1050537	1050634
ENSE00003519964	1010729	1010863
ENSE00003533494	1056998	1057102
ENSE00003550647	1125183	1125367
ENSE00003568874	1009679	1009784
ENSE00003594718	1013105	1013164
ENSE00003599823	1050050	1050181
ENSE00003622179	1079330	1079390
ENSE00003649730	1100637	1100735
ENSE00003655979	1069969	1070090
ENSE00003667923	1007165	1007312
ENSE00003694009	1056035	1056109
ENSE00003694157	1072614	1072754

Expression profiles

Bgee: expression breadth ubiquitous, 144 present calls, max score 98.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.6049 / max 431.3695, expressed in 1772 samples.

FANTOM5 promoters (30 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163680	16.1822	1616
163667	11.2052	1649
163691	1.6477	378
163692	1.2027	396
163656	1.1252	135
163668	0.8398	524
163654	0.8157	223
163685	0.8067	337
163669	0.7053	444
163678	0.5663	158

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
superior frontal gyrus	UBERON:0002661	98.80	gold quality
right frontal lobe	UBERON:0002810	98.63	gold quality
anterior cingulate cortex	UBERON:0009835	98.51	gold quality
temporal lobe	UBERON:0001871	98.48	gold quality
frontal cortex	UBERON:0001870	98.46	gold quality
amygdala	UBERON:0001876	98.46	gold quality
primary visual cortex	UBERON:0002436	98.46	gold quality
frontal lobe	UBERON:0016525	98.46	gold quality
right uterine tube	UBERON:0001302	98.37	gold quality
cerebral cortex	UBERON:0000956	98.36	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.34	gold quality
nucleus accumbens	UBERON:0001882	98.32	gold quality
prefrontal cortex	UBERON:0000451	98.29	gold quality
caudate nucleus	UBERON:0001873	98.25	gold quality
corpus callosum	UBERON:0002336	98.18	gold quality
Ammon’s horn	UBERON:0001954	98.12	gold quality
putamen	UBERON:0001874	98.09	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.08	gold quality
cortical plate	UBERON:0005343	97.98	gold quality
mucosa of transverse colon	UBERON:0004991	97.96	gold quality
transverse colon	UBERON:0001157	97.91	gold quality
descending thoracic aorta	UBERON:0002345	97.73	gold quality
hypothalamus	UBERON:0001898	97.69	gold quality
brain	UBERON:0000955	97.60	gold quality
ascending aorta	UBERON:0001496	97.52	gold quality
thoracic aorta	UBERON:0001515	97.52	gold quality
apex of heart	UBERON:0002098	97.52	gold quality
right coronary artery	UBERON:0001625	97.33	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.30	gold quality
right lung	UBERON:0002167	97.29	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	28.65
E-HCAD-25	yes	16.89
E-HCAD-30	no	252.76
E-ANND-3	no	2.65

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

156 targeting ABR, 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-4283	100.00	66.42	2097
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-185-3P	99.95	67.01	1743
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-4731-5P	99.89	67.23	2537

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 4)

• su(f) is required for the cleavage of pre-mRNA during mRNA 3’ end formation (PMID:12149458)
• During vestibular morphogenesis, Abr and Bcr play complementary roles. Small Rho-related GTPases like Abr and Bcr are important for balance and motor coordination. (PMID:11921339)
• ABR depletion leads to G2/M accumulation in human embryonic stem cells. Centrosome dynamics and mitotic fidelity are compromised upon ABR depletion. When mitosis progresses without ABR, human embryonic stem cells show a high incidence of aneuploidy. (PMID:28579391)
• The knockdown of GULP1 and ABR using siRNAs decreased phagocytosis by 40%. (PMID:31516309)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ABR	ENSDARG00000059587
danio_rerio	abr	ENSDARG00000095180
mus_musculus	Abr	ENSMUSG00000017631
rattus_norvegicus	Abr	ENSRNOG00000056837
drosophila_melanogaster	RhoGAP1A	FBGN0025836

Paralogs (1): BCR (ENSG00000186716)

Protein

Protein identifiers

Active breakpoint cluster region-related protein — Q12979 (reviewed: Q12979)

All UniProt accessions (14): Q12979, A0A0D9SGD7, A0A1C7CYZ0, B7Z683, I3L0R7, I3L1U8, I3L259, I3L2C0, I3L2L3, I3L2P5, I3L379, I3L3W0, I3L4Y1, I3NI05

UniProt curated annotations — full annotation on UniProt →

Function. Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins. The C-terminus is a GTPase-activating protein domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. Accelerates the intrinsic rate of GTP hydrolysis of RAC1 or CDC42, leading to down-regulation of the active GTP-bound form. The central Dbl homology (DH) domain functions as a guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form. Functions as an important negative regulator of neuronal RAC1 activity. Regulates macrophage functions such as CSF-1 directed motility and phagocytosis through the modulation of RAC1 activity.

Subunit / interactions. Interacts with DLG4.

Subcellular location. Cell projection. Dendritic spine. Axon. Synapse.

Tissue specificity. Highly enriched in the brain. Much weaker expression in heart, lung and muscle.

Domain organisation. The central Dbl homology (DH) domain functions as a guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form. The C-terminus is a Rho-GAP domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. The protein has a unique structure having two opposing regulatory activities toward small GTP-binding proteins.

Isoforms (4)

UniProt ID	Names	Canonical?
Q12979-1	Long	yes
Q12979-2	Short
Q12979-3	3
Q12979-4	4

RefSeq proteins (7): NP_001083, NP_001153218, NP_001243776, NP_001269078, NP_001309769, NP_001309770, NP_068781* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR000198	RhoGAP_dom	Domain
IPR000219	DH_dom	Domain
IPR001331	GDS_CDC24_CS	Conserved_site
IPR001849	PH_domain	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR035892	C2_domain_sf	Homologous_superfamily
IPR035899	DBL_dom_sf	Homologous_superfamily
IPR037769	Abr/Bcr	Family
IPR037865	ABR_PH	Domain

Pfam: PF00168, PF00620, PF00621, PF19057

UniProt features (22 total): sequence conflict 5, domain 4, splice variant 4, mutagenesis site 3, chain 1, sequence variant 1, region of interest 1, compositionally biased region 1, site 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12979-F1	79.10	0.43

Functional residue map

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

Catalytic / active sites (1): 683 (arginine finger; crucial for gtp hydrolysis by stabilizing the transition state)

Post-translational modifications (1): 57

Mutagenesis-validated functional residues (3):

Position	Phenotype
683	reduces gap activity. loss of gap activity; when associated with a-795.
795	loss of gap activity; when associated with a-683.
859	abolishes interaction with dlg4. no effect on synaptic localization.

Function

Pathways and Gene Ontology

Reactome pathways

18 pathways

ID	Pathway
R-HSA-193648	NRAGE signals death through JNK
R-HSA-416482	G alpha (12/13) signalling events
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013026	RHOB GTPase cycle
R-HSA-9013106	RHOC GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013404	RAC2 GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-193704	p75 NTR receptor-mediated signalling
R-HSA-194315	Signaling by Rho GTPases
R-HSA-204998	Cell death signalling via NRAGE, NRIF and NADE
R-HSA-372790	Signaling by GPCR
R-HSA-388396	GPCR downstream signalling
R-HSA-73887	Death Receptor Signaling
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 0 (showing top):

GO Biological Process (8): small GTPase-mediated signal transduction (GO:0007264), modulation of chemical synaptic transmission (GO:0050804), regulation of small GTPase mediated signal transduction (GO:0051056), activation of GTPase activity (GO:0090630), protein phosphorylation (GO:0006468), signal transduction (GO:0007165), intracellular signal transduction (GO:0035556), positive regulation of GTPase activity (GO:0043547)

GO Molecular Function (4): guanyl-nucleotide exchange factor activity (GO:0005085), GTPase activator activity (GO:0005096), protein serine/threonine kinase activity (GO:0004674), protein binding (GO:0005515)

GO Cellular Component (8): cytosol (GO:0005829), membrane (GO:0016020), axon (GO:0030424), dendritic spine (GO:0043197), Schaffer collateral - CA1 synapse (GO:0098685), glutamatergic synapse (GO:0098978), cell projection (GO:0042995), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
RHO GTPase cycle	7
Signal Transduction	3
Cell death signalling via NRAGE, NRIF and NADE	1
GPCR downstream signalling	1
Death Receptor Signaling	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
p75 NTR receptor-mediated signalling	1
Signaling by GPCR	1
Signaling by Rho GTPases	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
GTPase activity	2
GTPase regulator activity	2
synapse	2
intracellular signaling cassette	1
chemical synaptic transmission	1
regulation of trans-synaptic signaling	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
positive regulation of GTPase activity	1
phosphorylation	1
protein modification process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
intracellular anatomical structure	1
signal transduction	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
GTP binding	1
GDP binding	1
enzyme activator activity	1
protein kinase activity	1
binding	1
cytoplasm	1
neuron projection	1
dendrite	1
neuron spine	1
postsynapse	1
cell junction	1

Protein interactions and networks

STRING

574 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABR	DPEP1	P16444	506
ABR	TIAM1	Q13009	453
ABR	CDC42	P21181	438
ABR	FEV	Q99581	419
ABR	RHOA	P06749	406
ABR	R3HDM4	Q96D70	403
ABR	BHLHA9	Q7RTU4	387
ABR	A0A087WZG4	A0A087WZG4	384
ABR	ARHGEF18	Q6ZSZ5	384
ABR	KSR1	Q8IVT5	384
ABR	JUN	P05412	382
ABR	ARHGDIA	P52565	359
ABR	SPAAR	A0A1B0GVQ0	343
ABR	ARHGEF2	Q92974	338
ABR	CHGB	P05060	333

IntAct

18 interactions, top by confidence:

A	B	Type	Score
TBK1	TTC4	psi-mi:“MI:0914”(association)	0.540
ABR	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
ABL1	ABR	psi-mi:“MI:0915”(physical association)	0.400
TRPV2	ABR	psi-mi:“MI:0915”(physical association)	0.370
TBK1	UBR5	psi-mi:“MI:0914”(association)	0.350
rep	B4GALT3	psi-mi:“MI:0914”(association)	0.350
	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
	HLA-C	psi-mi:“MI:0914”(association)	0.350
ARRDC3	ESYT2	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC27A1	RIMOC1	psi-mi:“MI:0914”(association)	0.350
SLC7A9	CDC7	psi-mi:“MI:0914”(association)	0.350
	RPS10-NUDT3	psi-mi:“MI:0914”(association)	0.350
EZR	EEF2K	psi-mi:“MI:2364”(proximity)	0.270
TOMM20	NUDT19	psi-mi:“MI:2364”(proximity)	0.270
FGFR1	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
ABR	ADRA1A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (49): ABR (Affinity Capture-RNA), ABR (Affinity Capture-RNA), ABR (Affinity Capture-MS), ABR (Affinity Capture-RNA), ABR (Affinity Capture-RNA), ABR (Biochemical Activity), ABR (Affinity Capture-RNA), ABR (Proximity Label-MS), ABR (Proximity Label-MS), ABR (Affinity Capture-RNA), ABR (Reconstituted Complex), ABR (Affinity Capture-RNA), ABR (Affinity Capture-MS), ABR (Affinity Capture-MS), ABR (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JTR4, A1A4S6, A2AWA9, A4FUD6, A4II46, A6H6A9, A6QNS3, A6QQZ7, O60890, P09851, P0CAX5, P20936, P23727, P26450, P27986, P50904, Q08DP6, Q12979, Q5R372, Q5R5M3, Q5R685, Q5R6F2, Q5R8I6, Q5RCC1, Q5RCW6, Q5SSL4, Q5T2T1, Q5U2Y3, Q5ZJ17, Q5ZLX4, Q5ZMW5, Q62696, Q63787, Q6Y5D8, Q6ZQ82, Q7YQL5, Q7YQL6, Q8AVG0, Q8BPU7, Q8K0F1

Diamond homologs: A0A0G2JTR4, A1A4S6, A2AB59, A2RUV4, A4IF90, A4II46, A6QNS3, A6X8Z5, A7KAX9, A7YY57, A8WRJ2, D3ZFJ3, E7EZG2, E7F3F0, F1LXF1, O14559, O94466, P11274, P15882, P30337, P34288, P38339, P46941, P52757, P55194, P81128, P97393, Q03070, Q08DP6, Q10164, Q12979, Q13017, Q15311, Q17QN0, Q20498, Q2M1Z3, Q3TBD2, Q3UIA2, Q52LW3, Q53QZ3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ABR	“down-regulates activity”	RAC1	“gtpase-activating protein”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	53
Likely pathogenic	16
Uncertain significance	115
Likely benign	12
Benign	7

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1340108	GRCh37/hg19 17p13.3(chr17:858365-1690452)x3	Pathogenic
144305	GRCh38/hg38 17p13.3(chr17:198748-1920952)x1	Pathogenic
145642	GRCh38/hg38 17p13.3-13.1(chr17:198748-7491129)x3	Pathogenic
145643	GRCh38/hg38 17p13.3(chr17:198748-2685361)x1	Pathogenic
146016	GRCh38/hg38 17p13.3(chr17:1209808-1931101)x3	Pathogenic
146265	GRCh38/hg38 17p13.3(chr17:847955-1641601)x3	Pathogenic
146594	GRCh38/hg38 17p13.3-13.2(chr17:226472-3655099)x1	Pathogenic
149499	GRCh38/hg38 17p13.3(chr17:1227392-2261993)x1	Pathogenic
154089	GRCh38/hg38 17p13.3-12(chr17:150732-14764202)x3	Pathogenic
154232	GRCh38/hg38 17p13.3(chr17:150732-3242868)x1	Pathogenic
154829	GRCh38/hg38 17p13.3(chr17:1113825-1641612)x3	Pathogenic
219022	GRCh37/hg19 17p13.3(chr17:48858-920692)x1	Pathogenic
2426763	NC_000017.10:g.(?882539)(1387567_?)del	Pathogenic
2445495	NC_000017.10:g.(?422368)(1945151_?)del	Pathogenic
253507	GRCh37/hg19 17p13.3-13.2(chr17:919381-4046915)x3	Pathogenic
2671597	Single allele	Pathogenic
2684825	GRCh37/hg19 17p13.3(chr17:526-2687966)x3	Pathogenic
2685056	GRCh37/hg19 17p13.3(chr17:1036887-1249924)x4	Pathogenic
2685590	GRCh37/hg19 17p13.3-13.2(chr17:526-3441645)x1	Pathogenic
3063485	GRCh37/hg19 17p13.3-13.2(chr17:9474-6017500)x1	Pathogenic
3063505	GRCh37/hg19 17p13.3(chr17:1041646-1305005)x3	Pathogenic
3063518	GRCh37/hg19 17p13.3(chr17:1070465-1413071)x1	Pathogenic
3243204	NC_000017.10:g.(?882539)(1565467_?)del	Pathogenic
3391858	GRCh37/hg19 17p13.3(chr17:908763-1516480)x3	Pathogenic
3391933	GRCh37/hg19 17p13.3-13.2(chr17:9475-3793447)x1	Pathogenic
393889	GRCh37/hg19 17p13.3(chr17:6160-2002365)	Pathogenic
394212	GRCh37/hg19 17p13.3-13.2(chr17:48858-3379400)x1	Pathogenic
394439	GRCh37/hg19 17p13.3(chr17:48858-2940028)x1	Pathogenic
442031	GRCh37/hg19 17p13.3-13.2(chr17:525-4151421)x3	Pathogenic
442755	GRCh37/hg19 17p13.3(chr17:525-2264023)x1	Pathogenic

SpliceAI

7691 predictions. Top by Δscore:

Variant	Effect	Δscore
17:1007311:CC:C	acceptor_gain	1.0000
17:1007312:CC:C	acceptor_gain	1.0000
17:1007312:CCTA:C	acceptor_loss	1.0000
17:1007313:C:CC	acceptor_gain	1.0000
17:1007313:CTAAG:C	acceptor_loss	1.0000
17:1009678:C:CC	donor_loss	1.0000
17:1009780:CAGGG:C	acceptor_gain	1.0000
17:1009781:AGGG:A	acceptor_gain	1.0000
17:1009782:GGG:G	acceptor_gain	1.0000
17:1009783:GG:G	acceptor_gain	1.0000
17:1009785:C:CC	acceptor_gain	1.0000
17:1010731:ATGC:A	donor_gain	1.0000
17:1010859:GTTAT:G	acceptor_gain	1.0000
17:1010860:TTAT:T	acceptor_gain	1.0000
17:1010861:TAT:T	acceptor_gain	1.0000
17:1010862:AT:A	acceptor_gain	1.0000
17:1010863:TCTG:T	acceptor_loss	1.0000
17:1010864:C:CC	acceptor_gain	1.0000
17:1010864:C:CG	acceptor_loss	1.0000
17:1010865:T:A	acceptor_loss	1.0000
17:1011842:TCA:T	donor_loss	1.0000
17:1011844:A:AC	donor_gain	1.0000
17:1011844:ACTGG:A	donor_gain	1.0000
17:1011845:C:A	donor_loss	1.0000
17:1011845:C:CA	donor_gain	1.0000
17:1011845:CTGG:C	donor_gain	1.0000
17:1011845:CTGGC:C	donor_gain	1.0000
17:1012684:CTACT:C	donor_loss	1.0000
17:1012685:TA:T	donor_loss	1.0000
17:1012686:A:AC	donor_gain	1.0000

AlphaMissense

5674 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:1006147:A:G	L838P	1.000
17:1006159:A:G	L834P	1.000
17:1007241:A:G	L805P	1.000
17:1007253:C:T	G801E	1.000
17:1007254:C:G	G801R	1.000
17:1007254:C:T	G801R	1.000
17:1007259:A:T	V799E	1.000
17:1007265:G:T	A797D	1.000
17:1007268:A:G	L796P	1.000
17:1007270:G:C	N795K	1.000
17:1007270:G:T	N795K	1.000
17:1007272:T:C	N795D	1.000
17:1007282:C:A	M791I	1.000
17:1007282:C:G	M791I	1.000
17:1007282:C:T	M791I	1.000
17:1007283:A:C	M791R	1.000
17:1007283:A:G	M791T	1.000
17:1007283:A:T	M791K	1.000
17:1007286:T:A	K790I	1.000
17:1007288:G:C	N789K	1.000
17:1007288:G:T	N789K	1.000
17:1007310:A:T	V782D	1.000
17:1010770:A:C	L732R	1.000
17:1010770:A:T	L732H	1.000
17:1010782:A:G	L728P	1.000
17:1010788:C:G	R726P	1.000
17:1010795:A:C	Y724D	1.000
17:1010797:A:G	L723P	1.000
17:1010799:C:A	K722N	1.000
17:1010799:C:G	K722N	1.000

dbSNP variants (sampled 300 via entrez): RS1000008256 (17:1181760 G>A,T), RS1000012169 (17:1037709 A>G), RS1000026558 (17:1171132 G>GC), RS1000034525 (17:1011484 G>C), RS1000043328 (17:1149593 T>G), RS1000043785 (17:1174535 T>A,C), RS1000057050 (17:1041844 C>T), RS1000075144 (17:1126004 G>C), RS1000080101 (17:1076209 A>C), RS1000100108 (17:1044054 G>A), RS1000115477 (17:1070761 G>A), RS1000153664 (17:1137256 C>A,G,T), RS1000166725 (17:1201838 G>A), RS1000188283 (17:1173792 A>C), RS1000201826 (17:1227420 T>C)

Disease associations

OMIM: gene MIM:600365 | disease phenotypes: MIM:189800, MIM:192350, MIM:613215

GenCC curated gene-disease

Mondo (3): preeclampsia (MONDO:0005081), VACTERL/vater association (MONDO:0008642), chromosome 17p13.3 duplication syndrome (MONDO:0013182)

Orphanet (3): Preeclampsia (Orphanet:275555), VACTERL/VATER association (Orphanet:887), 17p13.3 microduplication syndrome (Orphanet:217385)

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST006288_280	Heel bone mineral density	2.000000e-15
GCST006288_348	Heel bone mineral density	2.000000e-07
GCST006288_353	Heel bone mineral density	1.000000e-08
GCST006979_646	Heel bone mineral density	4.000000e-53
GCST007203_8	Total cholesterol levels	4.000000e-06
GCST008163_383	Height	2.000000e-06
GCST009441_5	Age-related cognitive decline (memory) (slope of z-scores)	2.000000e-06
GCST90000025_113	Appendicular lean mass	7.000000e-15

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0004574	total cholesterol measurement
EFO:0007710	cognitive decline measurement
EFO:0004980	appendicular lean mass

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D011225	Pre-Eclampsia	C12.050.703.395.249
C567705	Chromosome 17p13.3 Duplication Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	5
Benzo(a)pyrene	affects methylation, decreases expression	5
Arsenic	affects methylation, decreases methylation, decreases expression, increases abundance	3
Cisplatin	affects response to substance, decreases expression	3
Valproic Acid	increases methylation, affects expression, increases expression	3
bisphenol A	increases methylation, decreases methylation, increases expression, affects cotreatment	2
cobaltous chloride	decreases expression	2
Air Pollutants	affects expression, increases abundance, increases expression	2
triphenyl phosphate	affects expression	1
benzo(e)pyrene	affects methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	affects methylation, increases methylation	1
cupric chloride	increases expression	1
muconaldehyde	decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
2-palmitoylglycerol	increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
bisphenol S	decreases methylation	1
jinfukang	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	increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Atrazine	decreases expression	1
Doxorubicin	decreases expression	1
Endosulfan	decreases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Lead	affects methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00117546	PHASE4	UNKNOWN	Cardiovascular and Autonomic Reactivity in Women With a History of Pre-eclampsia
NCT00567957	PHASE4	UNKNOWN	Remifentanil for General Anesthesia in Preeclamptics
NCT01030627	PHASE4	COMPLETED	Treatment Approaches to Preeclampsia
NCT01352234	PHASE4	COMPLETED	Comparison of Doses of Acetylsalicylic Acid in Women With Previous History of Preeclampsia
NCT01361425	PHASE4	UNKNOWN	Anti-Hypertensive Treatment In Stable Pregnant Women With Severe Pre-Eclampsia (Metildopape)
NCT01729468	PHASE4	COMPLETED	Prevention of Pre-eclampsia and SGA by Low-Dose Aspirin in Nulliparous Women With Abnormal First-trimester Uterine Artery Dopplers
NCT01761916	PHASE4	COMPLETED	Clonidine Versus Captopril for Treatment of Postpartum Very High Blood Pressure
NCT01912677	PHASE4	COMPLETED	Oral Antihypertensive Regimens for Management of Hypertension in Pregnancy
NCT02025426	PHASE4	TERMINATED	Phenylephrine Versus Ephedrine in Pre-eclampsia
NCT02091401	PHASE4	COMPLETED	A Trial Comparing Treatment With the Springfusor Infusion Pump to the IV Magnesium Sulfate Regimen
NCT02163655	PHASE4	COMPLETED	Diuretics for Postpartum High Blood Pressure in Preeclampsia
NCT02338687	PHASE4	COMPLETED	Low Dose Calcium to Prevent Preeclampsia
NCT02396030	PHASE4	TERMINATED	Different Schemes of Magnesium Sulfate for Preeclampsia
NCT02531490	PHASE4	UNKNOWN	Early Vascular Adjustments During Hypertensive Pregnancy
NCT02699827	PHASE4	COMPLETED	Adding MgSO4 to Epidural Levobupivacaine in CS for Patients With Preeclampsia
NCT02835339	PHASE4	COMPLETED	Magnesium Sulfate in Obese Preeclamptics
NCT02891174	PHASE4	COMPLETED	The Effect of Ibuprofen on Post-partum Blood Pressure in Women With Hypertensive Disorders of Pregnancy
NCT02911701	PHASE4	COMPLETED	Effect of Acetaminophen on Postpartum Blood Pressure Control in Preeclampsia With Severe Features
NCT03171480	PHASE4	COMPLETED	Use of Nitrous Oxide Donor for Labor Induction in Women With PreEclampsia
NCT03233880	PHASE4	UNKNOWN	Impact of Antichlamydial Treatment on the Rate of Preeclampsia
NCT03237000	PHASE4	UNKNOWN	Effect of Administering Intravenous Magnesium Sulfate on Fetal Cardiotocography and Neonatal Outcome in Preeclamptic Patients
NCT03506724	PHASE4	COMPLETED	Response to Anti-hypertensives in Pregnant and Postpartum Patients
NCT03674606	PHASE4	COMPLETED	Trial of Early Screening Test for Pre-eclampsia and Growth Restriction
NCT03735433	PHASE4	TERMINATED	The Effect of Two Aspirin Dosing Strategies for Obese Women at High Risk for Preeclampsia
NCT03824119	PHASE4	UNKNOWN	Postpartum NSAIDS and Maternal Hypertension
NCT04051567	PHASE4	UNKNOWN	Low-dose Aspirin for Prevention of Adverse Pregnancy Outcomes in Twin Pregnancies
NCT04077853	PHASE4	COMPLETED	Progesterone in Expectantly Managed Early-onset Preeclampsia
NCT04158830	PHASE4	WITHDRAWN	Aspirin (ASA) Therapy and Preeclampsia Prevention
NCT04424693	PHASE4	UNKNOWN	Comparing the Incidence of Preeclampsia Between Pregnant Women Receiving Tdap Vaccinations at Week 28 or at Week 36
NCT04631627	PHASE4	UNKNOWN	Early Prediction and Randomised Prevention of Preeclampsia With Low Dose Aspirin in Chinese Cohort
NCT04656665	PHASE4	UNKNOWN	The Effectiveness of Aspirin on Preventing Pre-eclampsia
NCT04797949	PHASE4	WITHDRAWN	Adherence to Universal Aspirin Compared to Screening Indicated Aspirin for Prevention of Preeclampsia
NCT04908982	PHASE4	UNKNOWN	Aspirin for the Prevention of Preeclampsia in Women With Stage 1 Hypertension
NCT05221164	PHASE4	UNKNOWN	162 mg of Aspirin for Prevention of Preeclampsia
NCT05294952	PHASE4	UNKNOWN	co Ihibtory Receptor in Preeclampsia
NCT05514847	PHASE4	ACTIVE_NOT_RECRUITING	Low Dose Aspirin for Preterm Preeclampsia Preventionmg/day Dose in High-risk Patients
NCT05586373	PHASE4	COMPLETED	Ibuprofen vs Dipyrone After C-section in Preeclampsia
NCT06069102	PHASE4	COMPLETED	Optimal Blood Pressure Treatment Thresholds Postpartum
NCT06107335	PHASE4	NOT_YET_RECRUITING	Effect of Albumin Versus Routine Care on Hemodynamic Response and Stability in Patients With Preeclampsia Guided by a Non-invasive Hemodynamic Monitoring System During Cesarean Delivery With Spinal Anesthesia
NCT06281665	PHASE4	RECRUITING	Treatment With Aspirin After Preeclampsia: TAP Trial