ABRAXAS2

Summary

ABRAXAS2 (abraxas 2, BRISC complex subunit, HGNC:28975) is a protein-coding gene on chromosome 10q26.13, encoding BRISC complex subunit Abraxas 2 (Q15018). Component of the BRISC complex, a multiprotein complex that specifically cleaves ‘Lys-63’-linked polyubiquitin, leaving the last ubiquitin chain attached to its substrates.

Enables microtubule binding activity and polyubiquitin modification-dependent protein binding activity. Involved in nuclear chromosome segregation; protein K63-linked deubiquitination; and response to ischemia. Located in cytosol; microtubule cytoskeleton; and midbody. Part of BRISC complex.

Source: NCBI Gene 23172 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 92 total — 25 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_032182

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28975
Approved symbol	ABRAXAS2
Name	abraxas 2, BRISC complex subunit
Location	10q26.13
Locus type	gene with protein product
Status	Approved
Aliases	Em:AC068896.4, ABRO1
Ensembl gene	ENSG00000165660
Ensembl biotype	protein_coding
OMIM	611144
Entrez	23172

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000298492, ENST00000899980, ENST00000899981

RefSeq mRNA: 1 — MANE Select: NM_032182 NM_032182

CCDS: CCDS31308

Canonical transcript exons

ENST00000298492 — 9 exons

Exon	Start	End
ENSE00001143109	124831349	124831463
ENSE00001161313	124834502	124836667
ENSE00001754860	124801819	124801901
ENSE00003257762	124819384	124819450
ENSE00003268481	124816576	124816612
ENSE00003336349	124806831	124806921
ENSE00003350823	124828756	124828875
ENSE00003433211	124829393	124829477
ENSE00003443443	124826595	124826785

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 95.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.5691 / max 376.7165, expressed in 1798 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
107549	17.5691	1798

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	95.20	gold quality
middle temporal gyrus	UBERON:0002771	90.38	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.12	gold quality
biceps brachii	UBERON:0001507	90.08	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.02	gold quality
deltoid	UBERON:0001476	86.94	gold quality
gastrocnemius	UBERON:0001388	86.93	gold quality
muscle of leg	UBERON:0001383	86.83	gold quality
calcaneal tendon	UBERON:0003701	86.54	gold quality
parietal pleura	UBERON:0002400	86.27	gold quality
visceral pleura	UBERON:0002401	86.26	gold quality
esophagus squamous epithelium	UBERON:0006920	86.23	gold quality
skeletal muscle organ	UBERON:0014892	86.16	gold quality
muscle organ	UBERON:0001630	86.15	gold quality
pleura	UBERON:0000977	85.96	gold quality
oocyte	CL:0000023	85.94	gold quality
gluteal muscle	UBERON:0002000	85.39	gold quality
upper leg skin	UBERON:0004262	85.32	gold quality
tibialis anterior	UBERON:0001385	85.31	silver quality
vastus lateralis	UBERON:0001379	85.27	gold quality
triceps brachii	UBERON:0001509	85.24	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.81	gold quality
heart right ventricle	UBERON:0002080	84.80	gold quality
squamous epithelium	UBERON:0006914	84.77	gold quality
quadriceps femoris	UBERON:0001377	84.74	gold quality
monocyte	CL:0000576	84.36	gold quality
leukocyte	CL:0000738	84.32	gold quality
mononuclear cell	CL:0000842	84.32	gold quality
ileal mucosa	UBERON:0000331	84.15	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	274.45
E-MTAB-7249	no	993.42
E-ANND-3	no	4.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

186 targeting ABRAXAS2, 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-5692A	100.00	74.40	6850
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778

Literature-anchored findings (GeneRIF, showing 8)

• Study identified Abro1 as a specific interactor of THAP5, a zinc finger transcription factor that is involved in G2/M control and apoptosis. (PMID:21195082)
• ABRO1 is a novel p53 regulator that plays an important role in tumor suppression and the DNA damage response (PMID:25283148)
• KIAA0157 allosterically activates a cognate deubiquitinating enzyme (DUB) partner and implicates super dimerization as a new regulatory mechanism underlying BRCC36 DUB activity. (PMID:26344097)
• In late S/G2 phase, the DNA damage-responsive E3 ligase RNF8 conjugates K63-linked ubiquitin chains to tankyrase 1, while in G1 phase such ubiquitin chains are removed by BRISC, an ABRO1/BRCC36-containing deubiquitinase complex. (PMID:27993934)
• pinpoint a direct interaction between the LNK SH2 domain and a phosphorylated tyrosine residue in KIAA0157 (Abraxas2), a unique and defining BRISC component. (PMID:30755420)
• FAM175B inhibited ATF4 ubiquitination and promoted esophageal squamous cell carcinomas (ESCCs) cell apoptosis in a p53-independent manner. FAM175B expression loss may be an early diagnostic biomarker in ESCC patients. (PMID:30854784)
• Transcriptional regulation of human abraxas brother protein 1 expression by yin yang 1. (PMID:32845162)
• ABRO1 stabilizes the deubiquitinase BRCC3 through inhibiting its degradation mediated by the E3 ubiquitin ligase WWP2. (PMID:33107021)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	abraxas2	ENSDARG00000098907
mus_musculus	Abraxas2	ENSMUSG00000030965
rattus_norvegicus	Abraxas2	ENSRNOG00000017222

Paralogs (1): ABRAXAS1 (ENSG00000163322)

Protein

Protein identifiers

BRISC complex subunit Abraxas 2 — Q15018 (reviewed: Q15018)

Alternative names: Abraxas brother protein 1, Protein FAM175B

All UniProt accessions (1): Q15018

UniProt curated annotations — full annotation on UniProt →

Function. Component of the BRISC complex, a multiprotein complex that specifically cleaves ‘Lys-63’-linked polyubiquitin, leaving the last ubiquitin chain attached to its substrates. May act as a central scaffold protein that assembles the various components of the BRISC complex and retains them in the cytoplasm. Plays a role in regulating the onset of apoptosis via its role in modulating ‘Lys-63’-linked ubiquitination of target proteins. Required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1. Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activities by enhancing its stability and cell surface expression. Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination. Required for normal induction of p53/TP53 in response to DNA damage. Independent of the BRISC complex, promotes interaction between USP7 and p53/TP53, and thereby promotes deubiquitination of p53/TP53, preventing its degradation and resulting in increased p53/TP53-mediated transcription regulation and p53/TP53-dependent apoptosis in response to DNA damage.

Subunit / interactions. Component of the BRISC complex, at least composed of ABRAXAS2, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. Interacts with BRCC3/BRCC36; the interaction is direct. Interacts with BABAM1. Does not interact with BRCA1. Interacts with SHMT1 and SHMT2; the interaction is direct. Identified in a complex with SHMT2 and the other subunits of the BRISC complex. The BRISC complex binds monoubiquitin and both ‘Lys-48’- and ‘Lys-63’-linked polyubiquitin. Identified in complexes with IFNAR1, IFNAR2 and SHMT2. Interacts with THAP5. Interacts with ATF4. Identified in a complex with p53/TP53 and USP7; interacts directly with both proteins. Interacts with NUMA1. Interacts with microtubule minus ends. Binds polyubiquitin.

Subcellular location. Cytoplasm. Nucleus. Cytoskeleton. Spindle pole.

Tissue specificity. Detected in heart muscle (at protein level). Detected in heart and muscle, and at much lower levels in brain.

Induction. Up-regulated in response to DNA damage. Up-regulated in myocardial infarction area (at protein level).

Similarity. Belongs to the FAM175 family. Abro1 subfamily.

RefSeq proteins (1): NP_115558* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR023238	FAM175	Family
IPR023240	BRISC_Abraxas2	Family
IPR037518	MPN	Domain

Pfam: PF21125

UniProt features (42 total): strand 10, helix 7, compositionally biased region 5, modified residue 5, mutagenesis site 5, region of interest 4, sequence conflict 2, chain 1, domain 1, turn 1, coiled-coil region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8PVY	ELECTRON MICROSCOPY	3.02
8PY2	ELECTRON MICROSCOPY	3.32
6R8F	ELECTRON MICROSCOPY	3.8
6H3C	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15018-F1	74.65	0.50

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 (5): 274, 280, 368, 372, 375

Mutagenesis-validated functional residues (5):

Position	Phenotype
11–12	slightly reduces interaction with bbrc36. abolishes interaction with shmt2. strongly reduces interactions with babam2 an
215–222	reduces interaction with shmt2, but has no effect on interaction with brcc3.
220	strongly reduces interaction with bbrc3; shmt2; babam2 and babam1; when associated with y-231. abolishes interaction wit
231	strongly reduces interaction with bbrc3; shmt2; babam2 and babam1; when associated with r-220. abolishes interaction wit
241	abolishes interaction with brcc3 and strongly reduces interaction with shmt2; babam2 and babam1; when associated with r-

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-5689901	Metalloprotease DUBs
R-HSA-392499	Metabolism of proteins
R-HSA-5688426	Deubiquitination
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 210 (showing top): E2F_Q4, GOBP_CHROMOSOME_ORGANIZATION, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_CHROMOSOME_LOCALIZATION, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, GGCNKCCATNK_UNKNOWN, GOCC_MICROTUBULE_ORGANIZING_CENTER, NFKB_Q6, GOBP_MITOTIC_SPINDLE_ASSEMBLY, GOBP_ORGANELLE_FISSION, AAACCAC_MIR140, GOBP_RESPONSE_TO_ISCHEMIA, KMCATNNWGGA_UNKNOWN

GO Biological Process (7): mitotic cell cycle (GO:0000278), response to ischemia (GO:0002931), chromosome segregation (GO:0007059), attachment of spindle microtubules to kinetochore (GO:0008608), cell division (GO:0051301), protein K63-linked deubiquitination (GO:0070536), mitotic spindle assembly (GO:0090307)

GO Molecular Function (3): microtubule binding (GO:0008017), polyubiquitin modification-dependent protein binding (GO:0031593), protein binding (GO:0005515)

GO Cellular Component (13): spindle pole (GO:0000922), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), microtubule (GO:0005874), ciliary transition zone (GO:0035869), ciliary basal body (GO:0036064), BRISC complex (GO:0070552), centrosome (GO:0005813), cytoskeleton (GO:0005856), midbody (GO:0030496), spindle pole centrosome (GO:0031616), microtubule minus-end (GO:0036449)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Deubiquitination	1
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
mitotic nuclear division	2
cell cycle process	2
cilium	2
microtubule organizing center	2
cell cycle	1
response to stress	1
microtubule binding	1
metaphase chromosome alignment	1
cellular process	1
protein deubiquitination	1
mitotic sister chromatid segregation	1
mitotic spindle organization	1
spindle assembly	1
tubulin binding	1
modification-dependent protein binding	1
binding	1
spindle	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
nuclear protein-containing complex	1
centriole	1
intracellular membraneless organelle	1
spindle pole	1
centrosome	1
microtubule end	1

Protein interactions and networks

STRING

828 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABRAXAS2	BABAM2	Q9NXR7	993
ABRAXAS2	BRCC3	P46736	992
ABRAXAS2	BABAM1	Q9NWV8	992
ABRAXAS2	UIMC1	Q96RL1	832
ABRAXAS2	BRCA1	P38398	814
ABRAXAS2	BOD1L1	Q8NFC6	668
ABRAXAS2	THAP5	Q7Z6K1	657
ABRAXAS2	SHMT2	P34897	630
ABRAXAS2	PSMD14	O00487	628
ABRAXAS2	USP7	Q93009	625
ABRAXAS2	USP50	Q70EL3	572
ABRAXAS2	RBBP8	Q99708	567
ABRAXAS2	PSMD7	P51665	526
ABRAXAS2	ZRANB3	Q5FWF4	513
ABRAXAS2	DNA2	P51530	512

IntAct

181 interactions, top by confidence:

A	B	Type	Score
TP53	MDM2	psi-mi:“MI:0914”(association)	1.000
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
ABRAXAS2	BRCC3	psi-mi:“MI:2364”(proximity)	0.690
BRCC3	ABRAXAS2	psi-mi:“MI:2364”(proximity)	0.690
BRCC3	ABRAXAS2	psi-mi:“MI:0915”(physical association)	0.690
ABRAXAS2	BRCC3	psi-mi:“MI:0915”(physical association)	0.690
BABAM2	BRCC3	psi-mi:“MI:0914”(association)	0.670
BABAM1	TNKS	psi-mi:“MI:0914”(association)	0.640
ARRDC1	NEDD4	psi-mi:“MI:0914”(association)	0.640
STK11	KDM4A	psi-mi:“MI:0914”(association)	0.640
AUP1	APOB	psi-mi:“MI:0914”(association)	0.610
DCUN1D1	ABRAXAS2	psi-mi:“MI:0915”(physical association)	0.560
ABRAXAS2	DCUN1D1	psi-mi:“MI:0915”(physical association)	0.560
XKRX	FAM234B	psi-mi:“MI:0914”(association)	0.530
DEF6	ARHGAP42	psi-mi:“MI:0914”(association)	0.530
TAFA4	NRP1	psi-mi:“MI:0914”(association)	0.530
SUV39H1	MAGEC1	psi-mi:“MI:0914”(association)	0.530
TNS1	SORBS3	psi-mi:“MI:0914”(association)	0.530
PNOC	CETN3	psi-mi:“MI:0914”(association)	0.530
ABRAXAS2	LAMC1	psi-mi:“MI:0914”(association)	0.530
ODF1	TCP1	psi-mi:“MI:0914”(association)	0.530
C9orf85	BRCC3	psi-mi:“MI:0914”(association)	0.530

BioGRID (192): FAM175B (Affinity Capture-Western), FAM175B (Reconstituted Complex), FAM175B (Affinity Capture-Western), USP7 (Affinity Capture-Western), TP53 (Affinity Capture-Western), USP7 (Reconstituted Complex), BABAM1 (Affinity Capture-Western), BRE (Affinity Capture-Western), BRCC3 (Affinity Capture-Western), LAMC1 (Affinity Capture-MS), THAP11 (Affinity Capture-MS), IGHG2 (Affinity Capture-MS), IGHG1 (Affinity Capture-MS), TRAF7 (Affinity Capture-MS), BRCC3 (Affinity Capture-MS)

ESM2 similar proteins: A0A8M3AJY3, A5WUN7, A6QLR3, B5X1P9, E2AB17, F1MJR8, F1QB81, M0R5D6, O00443, O43310, O60291, P03122, P11299, P15304, P42859, P51111, P59438, Q15018, Q1HKZ5, Q1LUT1, Q1LVP6, Q28HX0, Q2PFD7, Q2T9I9, Q3TCJ1, Q3TEL6, Q3UPF5, Q535K8, Q5E9P1, Q5I0F1, Q5RD34, Q5VUB5, Q5XIQ4, Q5ZHS0, Q61194, Q6GR31, Q6INH1, Q6P4W0, Q6PEE2, Q6UWZ7

Diamond homologs: A0A8M3AJY3, A6QLR3, B5X1P9, Q15018, Q1LVP6, Q28HX0, Q3TCJ1, Q5E9P1, Q5I0F1, Q5ZHS0, Q6GR31, Q6P4W0, Q6UWZ7, Q8BPZ8, E2AB17

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 172 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
Protein-protein interactions at synapses	6	15.3×	4e-04
Neurexins and neuroligins	8	15.2×	3e-05
Assembly and cell surface presentation of NMDA receptors	6	14.6×	4e-04
RHOQ GTPase cycle	8	13.9×	3e-05
RND3 GTPase cycle	5	12.5×	4e-03
RHOJ GTPase cycle	6	11.6×	1e-03
Cell death signalling via NRAGE, NRIF and NADE	5	10.6×	6e-03
RHOC GTPase cycle	7	9.8×	8e-04

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	6	22.8×	8e-05
receptor clustering	5	20.4×	8e-04
establishment of protein localization	5	14.1×	3e-03
response to ionizing radiation	5	13.4×	4e-03
protein-containing complex assembly	11	8.2×	6e-05
regulation of small GTPase mediated signal transduction	8	7.5×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	25
Likely pathogenic	1
Uncertain significance	59
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (26)

Variant ID	HGVS	Classification
146789	GRCh38/hg38 10q26.13-26.3(chr10:124473108-133620609)x1	Pathogenic
147735	GRCh38/hg38 10q26.13-26.2(chr10:124032888-127368827)x3	Pathogenic
148580	GRCh38/hg38 10q26.13-26.3(chr10:124834858-133622588)x1	Pathogenic
149417	GRCh38/hg38 10q26.13-26.3(chr10:122881207-133620609)x1	Pathogenic
150499	GRCh38/hg38 10q26.12-26.3(chr10:120970558-133622588)x1	Pathogenic
1527609	GRCh37/hg19 10q26.12-26.3(chr10:122343861-135427143)	Pathogenic
154670	GRCh38/hg38 10q26.13-26.3(chr10:121918547-133620674)x1	Pathogenic
155477	GRCh38/hg38 10q26.13-26.3(chr10:123576393-133613639)x1	Pathogenic
155556	GRCh38/hg38 10q26.13-26.3(chr10:123986772-133613639)x1	Pathogenic
219035	GRCh37/hg19 10q26.13-26.3(chr10:123731209-135353867)x1	Pathogenic
2580338	GRCh37/hg19 10q26.13-26.3(chr10:124895517-135440296)x1	Pathogenic
3063175	GRCh37/hg19 10q26.13-26.3(chr10:125987494-135427143)x1	Pathogenic
395627	GRCh37/hg19 10q26.13-26.3(chr10:124147428-135370736)x1	Pathogenic
4279490	GRCh37/hg19 10q26.11-26.3(chr10:120998462-135427143)x1	Pathogenic
4682770	GRCh37/hg19 10q26.13-26.3(chr10:126513306-135427143)x1	Pathogenic
563796	GRCh37/hg19 10q26.13-26.3(chr10:125450893-135427143)x1	Pathogenic
563797	GRCh37/hg19 10q26.12-26.3(chr10:123019239-135427143)x1	Pathogenic
563798	GRCh37/hg19 10q26.12-26.3(chr10:122509781-135427143)x1	Pathogenic
563799	GRCh37/hg19 10q26.11-26.3(chr10:121269222-135427143)x3	Pathogenic
57447	GRCh38/hg38 10q26.13-26.3(chr10:123307835-133620674)x1	Pathogenic
58820	GRCh38/hg38 10q26.13-26.2(chr10:122826743-126730948)x1	Pathogenic
58821	GRCh38/hg38 10q26.13-26.2(chr10:122973296-128210291)x1	Pathogenic
59728	GRCh38/hg38 10q26.11-26.3(chr10:117866565-133554210)x3	Pathogenic
688100	GRCh37/hg19 10q26.13-26.3(chr10:124988334-135427143)x3	Pathogenic
815379	GRCh37/hg19 10q26.11-26.3(chr10:119996339-135427143)x3	Pathogenic
1527608	GRCh37/hg19 10q26.12-26.3(chr10:122125760-135062972)	Likely pathogenic

SpliceAI

1013 predictions. Top by Δscore:

Variant	Effect	Δscore
10:124806922:G:GG	donor_gain	1.0000
10:124819382:A:AG	acceptor_gain	1.0000
10:124819383:G:GG	acceptor_gain	1.0000
10:124826590:TTCA:T	acceptor_loss	1.0000
10:124826591:TCAGA:T	acceptor_loss	1.0000
10:124826592:CA:C	acceptor_loss	1.0000
10:124826593:A:AG	acceptor_gain	1.0000
10:124826593:AGA:A	acceptor_loss	1.0000
10:124826594:G:GC	acceptor_gain	1.0000
10:124826594:GA:G	acceptor_gain	1.0000
10:124826594:GAA:G	acceptor_gain	1.0000
10:124826594:GAAA:G	acceptor_gain	1.0000
10:124826783:AAGG:A	donor_loss	1.0000
10:124826784:AGG:A	donor_loss	1.0000
10:124826786:GTAAA:G	donor_loss	1.0000
10:124826787:T:G	donor_loss	1.0000
10:124828754:A:G	acceptor_loss	1.0000
10:124828755:G:GC	acceptor_loss	1.0000
10:124828873:TGGGT:T	donor_loss	1.0000
10:124828874:GG:G	donor_gain	1.0000
10:124828875:GG:G	donor_gain	1.0000
10:124828876:G:GA	donor_loss	1.0000
10:124828876:G:GG	donor_gain	1.0000
10:124828877:T:TT	donor_loss	1.0000
10:124828878:AAGTT:A	donor_loss	1.0000
10:124829379:T:A	acceptor_gain	1.0000
10:124829383:T:TA	acceptor_gain	1.0000
10:124829388:TCCA:T	acceptor_loss	1.0000
10:124829389:CCA:C	acceptor_loss	1.0000
10:124829390:CA:C	acceptor_loss	1.0000

AlphaMissense

2771 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:124806834:G:A	G26R	1.000
10:124806834:G:C	G26R	1.000
10:124806838:T:C	F27S	1.000
10:124806846:G:A	G30R	1.000
10:124806846:G:C	G30R	1.000
10:124806847:G:A	G30E	1.000
10:124826604:G:A	G93R	1.000
10:124826604:G:C	G93R	1.000
10:124826604:G:T	G93W	1.000
10:124826605:G:A	G93E	1.000
10:124826607:T:A	W94R	1.000
10:124826607:T:C	W94R	1.000
10:124828814:T:C	Y173H	1.000
10:124801848:G:C	G7R	0.999
10:124801849:G:A	G7D	0.999
10:124801860:A:C	S11R	0.999
10:124801862:T:A	S11R	0.999
10:124801862:T:G	S11R	0.999
10:124806835:G:A	G26E	0.999
10:124806841:T:C	L28S	0.999
10:124806847:G:T	G30V	0.999
10:124806882:G:C	D42H	0.999
10:124806883:A:C	D42A	0.999
10:124806883:A:G	D42G	0.999
10:124806883:A:T	D42V	0.999
10:124826605:G:T	G93V	0.999
10:124826610:T:G	Y95D	0.999
10:124826620:G:C	R98P	0.999
10:124826674:T:C	L116P	0.999
10:124826710:T:C	L128P	0.999

dbSNP variants (sampled 300 via entrez): RS1000067841 (10:124824042 T>C), RS1000091731 (10:124803227 A>C), RS1000124484 (10:124827483 CGG>C), RS1000176077 (10:124831731 T>C,G), RS1000427073 (10:124827148 G>A,T), RS1000461023 (10:124829229 A>C), RS1000613064 (10:124831503 A>G), RS1000654684 (10:124821655 C>T), RS1000660444 (10:124837030 T>A,C), RS1000669215 (10:124836344 C>T), RS1000724174 (10:124820309 A>G), RS1000764775 (10:124828769 A>C), RS1000872672 (10:124801929 G>C,T), RS1000894547 (10:124809257 G>A), RS1000913147 (10:124829953 A>C)

Disease associations

OMIM: gene MIM:611144 | disease phenotypes: MIM:609625

GenCC curated gene-disease

Mondo (1): distal 10q deletion syndrome (MONDO:0012315)

Orphanet (1): Distal deletion 10q syndrome (Orphanet:96148)

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST003830_24	Response to bronchodilator in chronic obstructive pulmonary disease (change in FEV1)	3.000000e-07
GCST004131_12	Inflammatory bowel disease	1.000000e-09
GCST004132_94	Crohn’s disease	3.000000e-06
GCST004133_33	Ulcerative colitis	1.000000e-06
GCST006014_18	Creatine kinase levels	4.000000e-08
GCST006661_312	Male-pattern baldness	6.000000e-21
GCST006870_6	Hippocampal tail volume	3.000000e-14
GCST006871_8	Total hippocampal volume	1.000000e-15
GCST006878_1	Dentate gyrus molecular layer volume (corrected for total hippocampal volume)	4.000000e-12
GCST006887_2	Hippocampal subfield CA1 volume	1.000000e-09
GCST006888_1	Hippocampal subfield CA3 volume	3.000000e-12
GCST006889_4	Hippocampal subfield CA4 volume	6.000000e-15
GCST006890_3	Dentate gyrus granule cell layer volume	9.000000e-15
GCST006891_2	Dentate gyrus molecular layer volume	2.000000e-10
GCST006979_613	Heel bone mineral density	1.000000e-10
GCST008839_43	Height	2.000000e-21
GCST009378_9	Bone mineral content	8.000000e-07
GCST010703_92	Brain morphology (MOSTest)	4.000000e-63
GCST012227_624	Hip circumference adjusted for BMI	1.000000e-08

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0005921	FEV change measurement
EFO:0004534	creatine kinase measurement
EFO:0005035	hippocampal volume
EFO:0009394	hippocampal CA1 volume
EFO:0009395	hippocampal CA3 volume
EFO:0009396	hippocampal CA4 volume
EFO:0009270	heel bone mineral density
EFO:0007621	bone mineral content measurement
EFO:0004346	neuroimaging measurement
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567182	Chromosome 10q26 Deletion Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Capzimin	IC50	340 nM	US-10005735: Inhibitors of RPN11

PubChem BioAssay actives

1 with measured affinity, of 1 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
8-sulfanyl-N-[2-(1,3-thiazol-2-yl)ethyl]quinoline-3-carboxamide	1802703: In Vitro BRCC36 Activity Assay from Article 10.1038/nchembio.2326: “Capzimin is a potent and specific inhibitor of proteasome isopeptidase Rpn11.”	ic50	2.3000	uM

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
deoxynivalenol	increases expression	1
sodium arsenite	decreases expression	1
zinc chromate	increases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, increases expression	1
K 7174	increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	decreases phosphorylation	1
Doxorubicin	decreases expression	1
Folic Acid	decreases expression	1
Ivermectin	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Rotenone	increases expression	1
T-2 Toxin	increases expression	1
Valproic Acid	decreases expression	1
Cadmium Chloride	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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