BCORL1

Summary

BCORL1 (BCL6 corepressor like 1, HGNC:25657) is a protein-coding gene on chromosome Xq26.1, encoding BCL-6 corepressor-like protein 1 (Q5H9F3). Transcriptional corepressor.

The protein encoded by this gene is a transcriptional corepressor that is found tethered to promoter regions by DNA-binding proteins. The encoded protein can interact with several different class II histone deacetylases to repress transcription. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 63035 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Shukla-Vernon syndrome (Strong, GenCC) — +3 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 719 total — 3 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 28
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 5 cancer types
• MANE Select transcript: NM_001379451

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25657
Approved symbol	BCORL1
Name	BCL6 corepressor like 1
Location	Xq26.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11362, BCoR-L1
Ensembl gene	ENSG00000085185
Ensembl biotype	protein_coding
OMIM	300688
Entrez	63035

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 nonsense_mediated_decay

ENST00000218147, ENST00000441294, ENST00000488135, ENST00000540052, ENST00000607874

RefSeq mRNA: 4 — MANE Select: NM_001379451 NM_001184772, NM_001379450, NM_001379451, NM_021946

CCDS: CCDS14616, CCDS94663

Canonical transcript exons

ENST00000540052 — 14 exons

Exon	Start	End
ENSE00000676448	130020985	130021150
ENSE00001155161	130022897	130022977
ENSE00001165987	130034455	130034676
ENSE00001435266	130024990	130025379
ENSE00001663385	130012578	130012668
ENSE00001666402	130012950	130016213
ENSE00001674915	130051860	130052016
ENSE00001683839	130037367	130037533
ENSE00001691280	130039137	130039282
ENSE00001694110	130050717	130050794
ENSE00002224260	130055854	130058071
ENSE00003789632	130028635	130028861
ENSE00003799629	130005188	130005317
ENSE00003915648	129982635	129982762

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 92.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.2509 / max 118.9985, expressed in 1764 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197541	7.8924	1700
197540	1.2141	667
197539	1.0113	526
197543	0.1332	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cervix squamous epithelium	UBERON:0006922	92.64	silver quality
cardia of stomach	UBERON:0001162	90.68	silver quality
vena cava	UBERON:0004087	90.63	silver quality
nipple	UBERON:0002030	90.24	gold quality
saphenous vein	UBERON:0007318	89.97	gold quality
ventral tegmental area	UBERON:0002691	89.44	silver quality
pylorus	UBERON:0001166	89.30	silver quality
cerebellar vermis	UBERON:0004720	89.28	silver quality
body of tongue	UBERON:0011876	89.22	silver quality
inferior vagus X ganglion	UBERON:0005363	88.70	gold quality
superior surface of tongue	UBERON:0007371	88.67	silver quality
pericardium	UBERON:0002407	88.55	gold quality
oocyte	CL:0000023	88.38	gold quality
tongue	UBERON:0001723	88.16	silver quality
trachea	UBERON:0003126	87.88	silver quality
renal medulla	UBERON:0000362	87.82	gold quality
dorsal root ganglion	UBERON:0000044	87.70	gold quality
pharyngeal mucosa	UBERON:0000355	87.63	silver quality
trigeminal ganglion	UBERON:0001675	87.17	silver quality
superior vestibular nucleus	UBERON:0007227	87.15	silver quality
medulla oblongata	UBERON:0001896	87.02	silver quality
secondary oocyte	CL:0000655	87.00	gold quality
blood vessel layer	UBERON:0004797	86.54	silver quality
synovial joint	UBERON:0002217	86.46	gold quality
subthalamic nucleus	UBERON:0001906	86.44	silver quality
placenta	UBERON:0001987	86.14	gold quality
pons	UBERON:0000988	86.11	silver quality
pancreatic ductal cell	CL:0002079	85.99	silver quality
dorsal plus ventral thalamus	UBERON:0001897	85.18	silver quality
mammary duct	UBERON:0001765	84.88	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

127 targeting BCORL1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-12118	100.00	65.88	1270
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-6127	100.00	66.76	2188
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-128-3P	99.95	71.17	2484

Literature-anchored findings (GeneRIF, showing 18)

• Dysregulated BCoR-L1 expression is associated with breast cancer (PMID:17697391)
• BCORL1 by genetic criteria is a novel candidate tumor suppressor gene, joining the growing list of genes recurrently mutated in acute myelogenous leukemia. (PMID:21989985)
• genetic association study in population in Italy: Data suggest BCORL1 mutations/single nucleotide polymorphisms are not associated with leukemic transformation of chronic myeloproliferative neoplasms (MPN) into acute myeloid leukemia (AML). [LETTER] (PMID:23793880)
• Data indicate that sequencing of BCOR and related BCORL1 genes in a cohort of 354 myelodysplastic syndromes (MDS) patients identified 4.2% and 0.8% of mutations respectively. (PMID:24047651)
• study concluded that in pediatric acute myeloid leukemia, BCOR and BCORL1 mutations rarely occur (PMID:25596268)
• BCORL1 knockdown up-regulates E-cadherin expression and subsequently inhibits cell migration and invasion of lung cancer cells. (PMID:26648304)
• Either endogenous BCORL1 silencing or ectopic BCORL1(Q1076H) expression mimicked the effects of a CRISPR/Cas9-edited BCORL1(Q1076H) locus. (PMID:29605720)
• We report five individuals from three pedigrees with phenotypes including intellectual disability, behavioral difficulties, and dysmorphic features who were found via whole exome sequencing to have variants in BCORL1. In silico analysis of these variants strongly suggests pathogenicity. We propose that hemizygous pathogenic variants in BCORL1 underlie a newly identified X-linked epigenetic syndrome. (PMID:30941876)
• Human X chromosome exome sequencing identifies BCORL1 as contributor to spermatogenesis. (PMID:32376790)
• patients with acquired Acquired pure red cell aplasia may have clonal gene mutations. The patients with BCOR and BCORL1 mutations may suggest a better response to IST compared with those with other mutations. (PMID:32594217)
• Age-Related Co-Expression of BCOR and BCORL1 mRNA in Acute Myeloid Leukemia. (PMID:32776737)
• [Clinical Characteristics and Prognostic Significance of BCOR/BCORL1 Gene Mutation in Patients with Myelodysplastic Syndromes]. (PMID:33283733)
• Shukla-Vernon Syndrome: A Second Family with a Novel Variant in the BCORL1 Gene. (PMID:33810051)
• Clinicopathological and genomic characterization of BCORL1-driven high-grade endometrial stromal sarcomas. (PMID:34302054)
• Major brain malformations: corpus callosum dysgenesis, agenesis of septum pellucidum and polymicrogyria in patients with BCORL1-related disorders. (PMID:34400773)
• BCOR and BCORL1 Mutations Drive Epigenetic Reprogramming and Oncogenic Signaling by Unlinking PRC1.1 from Target Genes. (PMID:35015684)
• Endometrial Stromal Sarcomas With BCOR Internal Tandem Duplication and Variant BCOR/BCORL1 Rearrangements Resemble High-grade Endometrial Stromal Sarcomas With Recurrent CDK4 Pathway Alterations and MDM2 Amplifications. (PMID:35499168)
• A hemizygous loss-of-function variant in BCORL1 is associated with male infertility and oligoasthenoteratozoospermia. (PMID:38342987)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	bcorl1	ENSDARG00000077912
mus_musculus	Bcorl1	ENSMUSG00000036959
rattus_norvegicus	Bcorl1	ENSRNOG00000005076
drosophila_melanogaster	CG14073	FBGN0036814

Paralogs (1): BCOR (ENSG00000183337)

Protein

Protein identifiers

BCL-6 corepressor-like protein 1 — Q5H9F3 (reviewed: Q5H9F3)

All UniProt accessions (4): Q5H9F3, A0A087X1F0, H7C4B2, V9GYD4

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional corepressor. May specifically inhibit gene expression when recruited to promoter regions by sequence-specific DNA-binding proteins such as BCL6. This repression may be mediated at least in part by histone deacetylase activities which can associate with this corepressor.

Subunit / interactions. Interacts with PCGF1, forming heterodimers. The PCGF1-BCORL1 heterodimeric complex interacts with the KDM2B-SKP1 heterodimeric complex to form a homotetrameric polycomb repression complex 1 (PRC1.1). Interacts with SKP1. Interacts with CTBP1, HDAC4, HDAC5 and HDAC7.

Subcellular location. Nucleus.

Tissue specificity. Detected in testis and prostate. Detected at lower levels in peripheral blood leukocytes and spleen. Mainly expressed in the spermatogonia and primary spermatocytes.

Disease relevance. Shukla-Vernon syndrome (SHUVER) [MIM:301029] An X-linked neurodevelopmental disorder manifesting in affected males with intellectual and learning disability, motor and language delay, autism spectrum disorder, attention deficit and hyperactivity disorder, and dysmorphic features. Some patients may have seizures and/or cerebellar atrophy on brain imaging. Carrier females may have mild disease manifestations. The disease may be caused by variants affecting the gene represented in this entry. Defects in BCORL1 may be a cause of male infertility due to oligoasthenoteratozoospermia. Affected individuals have a reduced sperm count, decreased progressive sperm motility, and a low proportion of morphologically normal sperm. In some cases, infertility is due to non-obstructive azoospermia.

Similarity. Belongs to the BCOR family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5H9F3-3	3	yes
Q5H9F3-1	1
Q5H9F3-4	4

RefSeq proteins (4): NP_001171701, NP_001366379, NP_001366380, NP_068765 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR032365	PUFD	Domain
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR038227	PUFD_som_sf	Homologous_superfamily
IPR047144	BCOR-like	Family

Pfam: PF12796, PF16553

UniProt features (67 total): sequence variant 13, compositionally biased region 12, region of interest 11, modified residue 7, strand 7, helix 4, repeat 3, cross-link 2, splice variant 2, mutagenesis site 2, chain 1, short sequence motif 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4HPM	X-RAY DIFFRACTION	1.85
5JH5	X-RAY DIFFRACTION	2.55

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5H9F3-F1	38.79	0.06

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 (9): 496, 599, 613, 1029, 1033, 1162, 1476, 747, 1092

Mutagenesis-validated functional residues (2):

Position	Phenotype
623–624	strongly reduced repressor activity. interferes with ctbp1 binding.
1739	slightly inhibits interaction with pcgf1.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 189 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, ACTGCAG_MIR173P, GTACAGG_MIR486, CCATCCA_MIR432, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, MODULE_205, LIAO_METASTASIS, GOCC_NUCLEAR_UBIQUITIN_LIGASE_COMPLEX, ACCGAGC_MIR423, GOBP_CHROMATIN_REMODELING, GOBP_HETEROCHROMATIN_ORGANIZATION, AGCATTA_MIR155, GOBP_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_UP, GOCC_TRANSFERASE_COMPLEX

GO Biological Process (2): negative regulation of transcription by RNA polymerase II (GO:0000122), chromatin organization (GO:0006325)

GO Molecular Function (2): transcription corepressor activity (GO:0003714), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), plasma membrane (GO:0005886)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of DNA-templated transcription	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
cellular component organization	1
transcription coregulator activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1306 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BCORL1	PCGF1	Q9BSM1	802
BCORL1	KDM2B	Q8NHM5	798
BCORL1	BCL6	P41182	786
BCORL1	RING1	Q06587	745
BCORL1	CTBP1	Q13363	736
BCORL1	SKP1	P34991	721
BCORL1	ASXL1	Q8IXJ9	716
BCORL1	HDAC7	Q8WUI4	685
BCORL1	ZRSR2	Q15696	658
BCORL1	PIGA	P37287	658
BCORL1	PHF6	Q8IWS0	654
BCORL1	HDAC9	Q9UKV0	652
BCORL1	HDAC4	P56524	630
BCORL1	STAG2	Q8N3U4	626
BCORL1	SETBP1	Q9Y6X0	625

IntAct

70 interactions, top by confidence:

A	B	Type	Score
RYBP	CSNK2A2	psi-mi:“MI:0914”(association)	0.900
RYBP	BMI1	psi-mi:“MI:0914”(association)	0.850
PCGF2	CBX4	psi-mi:“MI:0914”(association)	0.840
RYBP	E2F6	psi-mi:“MI:0914”(association)	0.740
RING1	CBX4	psi-mi:“MI:0914”(association)	0.730
RNF2	E2F6	psi-mi:“MI:0914”(association)	0.730
CTBP1	CBX4	psi-mi:“MI:0914”(association)	0.700
RNF2	CBX4	psi-mi:“MI:0914”(association)	0.660
PCGF6	CBX4	psi-mi:“MI:0914”(association)	0.640
YAF2	E2F6	psi-mi:“MI:0914”(association)	0.640
PCGF1	CBX4	psi-mi:“MI:0914”(association)	0.530
BAG4	DNAJC13	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
SNAPC4	KDM5C	psi-mi:“MI:0914”(association)	0.530
CBX6	ZBTB24	psi-mi:“MI:0914”(association)	0.530
FBL	GXYLT2	psi-mi:“MI:0914”(association)	0.350
KDM2B	H2AX	psi-mi:“MI:0914”(association)	0.350
H2BC21	SMCHD1	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
hspa1a_hspa1b_human-1	SHTN1	psi-mi:“MI:0914”(association)	0.350
ZCCHC10	C1orf226	psi-mi:“MI:0914”(association)	0.350

BioGRID (137): BCORL1 (Affinity Capture-MS), BCORL1 (Affinity Capture-MS), BCORL1 (Affinity Capture-MS), BCORL1 (Affinity Capture-MS), BCORL1 (Synthetic Lethality), BCORL1 (Proximity Label-MS), BCORL1 (Proximity Label-MS), BCORL1 (Affinity Capture-MS), BCORL1 (Affinity Capture-MS), BCORL1 (Affinity Capture-MS), BCORL1 (Affinity Capture-MS), BCORL1 (Affinity Capture-MS), BCORL1 (Affinity Capture-MS), BCORL1 (Affinity Capture-MS), BCORL1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GTH6, A0A1B0GUW6, A0A1D5RMD1, A2AQH4, A4FU49, A6NJ88, C4P6S0, D3YU32, E9PAV3, F1QU13, I3L273, J3KML8, P70670, Q32L62, Q3V0E1, Q3V3Q4, Q4R729, Q5H9F3, Q5QJ38, Q5SWP3, Q5U4C1, Q5VWK0, Q5VYM1, Q68DN1, Q6AZ54, Q7TSG5, Q810T2, Q8CH19, Q8K4E0, Q8N3K9, Q8N5Q1, Q8NDH2, Q8TCU4, Q8WNU4, Q8WWL7, Q920R4, Q921B4, Q923B3, Q96JA4, Q96M34

Diamond homologs: A2AQH4, A2AS55, A6NGH8, A6QR20, O14974, Q2T9W8, Q499M5, Q5H9F3, Q641X1, Q6P6B7, Q6W2J9, Q86WC6, Q8CGN4, Q9BQI6, Q9D119, Q9UU77, Q9XZC0, A4II29, A5WVX9, B4E2M5, D3Z7P3, E9PTT0, G5EGA3, O83515, O94925, P13264, Q01317, Q15653, Q21920, Q3SX45, Q3U0L2, Q4FE45, Q4JHE0, Q502K3, Q54HW1, Q5U5A6, Q6NSI1, Q6NY19, Q7T3Y0, Q7Z6K4

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
BCORL1	“up-regulates activity”	HDAC4	binding
BCORL1	“up-regulates activity”	HDAC5	binding
BCORL1	“up-regulates activity”	HDAC7	binding
BCORL1	“up-regulates activity”	CTBP1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 77 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
SUMOylation of DNA methylation proteins	5	56.9×	3e-06
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	10	50.9×	1e-12
Transcriptional Regulation by E2F6	8	39.7×	4e-09
SUMOylation of transcription cofactors	6	24.7×	2e-05
SUMOylation of RNA binding proteins	5	20.2×	3e-04
Regulation of PTEN gene transcription	6	18.1×	8e-05
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	6	14.9×	2e-04
SUMOylation of chromatin organization proteins	5	13.4×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
chromatin remodeling	11	11.3×	2e-06
protein stabilization	10	9.4×	3e-05

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 5 cancer types — AML, COADREAD, HGGNOS, NBL, PAAD.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	4
Uncertain significance	363
Likely benign	69
Benign	13

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
2499567	NM_001379451.1(BCORL1):c.4324C>T (p.Gln1442Ter)	Pathogenic
2687797	NM_001379451.1(BCORL1):c.2615T>G (p.Val872Gly)	Pathogenic
2687871	NM_001379451.1(BCORL1):c.4171G>A (p.Gly1391Arg)	Pathogenic
1722312	NM_001379451.1(BCORL1):c.1562_1563del (p.Leu521fs)	Likely pathogenic
638170	NM_001379451.1(BCORL1):c.95C>T (p.Pro32Leu)	Likely pathogenic
800335	NM_001379451.1(BCORL1):c.2242C>T (p.Gln748Ter)	Likely pathogenic
973685	NM_001379451.1(BCORL1):c.3793C>T (p.Arg1265Cys)	Likely pathogenic

SpliceAI

2876 predictions. Top by Δscore:

Variant	Effect	Δscore
X:129982760:G:GT	donor_gain	1.0000
X:130005186:AGGG:A	acceptor_gain	1.0000
X:130005187:GGGG:G	acceptor_gain	1.0000
X:130005314:AGAG:A	donor_loss	1.0000
X:130005315:GAG:G	donor_gain	1.0000
X:130005316:AG:A	donor_loss	1.0000
X:130005317:GG:G	donor_loss	1.0000
X:130005318:G:GC	donor_loss	1.0000
X:130012557:T:TA	acceptor_gain	1.0000
X:130012564:A:AG	acceptor_gain	1.0000
X:130012565:T:G	acceptor_gain	1.0000
X:130012571:A:AG	acceptor_gain	1.0000
X:130012571:AT:A	acceptor_gain	1.0000
X:130012572:T:G	acceptor_gain	1.0000
X:130012572:T:TA	acceptor_gain	1.0000
X:130012576:A:AG	acceptor_gain	1.0000
X:130012577:G:GG	acceptor_gain	1.0000
X:130012664:CCAAG:C	donor_loss	1.0000
X:130012665:CAAG:C	donor_loss	1.0000
X:130012666:AAGGT:A	donor_loss	1.0000
X:130012667:AGGT:A	donor_loss	1.0000
X:130012669:G:GC	donor_loss	1.0000
X:130012670:T:G	donor_loss	1.0000
X:130012946:GCAG:G	acceptor_loss	1.0000
X:130012948:A:AC	acceptor_loss	1.0000
X:130012949:G:GT	acceptor_loss	1.0000
X:130020983:A:AG	acceptor_gain	1.0000
X:130020984:G:GA	acceptor_gain	1.0000
X:130020984:GT:G	acceptor_gain	1.0000
X:130021147:G:GT	donor_gain	1.0000

AlphaMissense

11503 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:130037485:T:C	L1475P	1.000
X:130014921:T:G	Y717D	0.999
X:130014927:G:A	G719R	0.999
X:130014927:G:C	G719R	0.999
X:130014928:G:A	G719E	0.999
X:130022935:T:C	F1216L	0.999
X:130022936:T:C	F1216S	0.999
X:130022937:T:A	F1216L	0.999
X:130022937:T:G	F1216L	0.999
X:130022939:T:A	I1217N	0.999
X:130022939:T:C	I1217T	0.999
X:130022948:T:A	V1220D	0.999
X:130028823:A:G	K1423E	0.999
X:130028825:G:C	K1423N	0.999
X:130028825:G:T	K1423N	0.999
X:130037419:A:T	D1453V	0.999
X:130037440:T:C	L1460P	0.999
X:130037448:G:C	A1463P	0.999
X:130037452:G:A	C1464Y	0.999
X:130037453:T:G	C1464W	0.999
X:130037476:T:C	L1472P	0.999
X:130037488:T:C	L1476P	0.999
X:130037527:G:T	G1489V	0.999
X:130039139:C:A	P1492Q	0.999
X:130039139:C:G	P1492R	0.999
X:130039142:T:A	V1493D	0.999
X:130039187:T:C	L1508P	0.999
X:130039190:T:C	L1509P	0.999
X:130039247:T:C	L1528P	0.999
X:130039274:T:C	F1537S	0.999

dbSNP variants (sampled 300 via entrez): RS1000019632 (X:130032731 T>A,C), RS1000077942 (X:130045442 G>A), RS1000079913 (X:130049706 T>C), RS1000248115 (X:129995683 A>C), RS1000249962 (X:130016237 G>A), RS1000263542 (X:130044276 T>C), RS1000308669 (X:129981507 G>C), RS1000387736 (X:129990982 T>C), RS1000396878 (X:130054109 G>A), RS1000413424 (X:129988721 G>A,C), RS1000476270 (X:130033248 A>T), RS1000502719 (X:130042114 T>G), RS1000515075 (X:130034849 A>G), RS1000599228 (X:130041804 T>A), RS1000610749 (X:130001830 G>A)

Disease associations

OMIM: gene MIM:300688 | disease phenotypes: MIM:301029, MIM:254500

GenCC curated gene-disease

Disease	Classification	Inheritance
Shukla-Vernon syndrome	Strong	X-linked
spermatogenic failure	Strong	X-linked
congenital anomaly of kidney and urinary tract	Moderate	X-linked
syndromic intellectual disability	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Shukla-Vernon syndrome	Limited	XL

Mondo (8): Shukla-Vernon syndrome (MONDO:0026727), neurodevelopmental disorder (MONDO:0700092), oligoasthenoteratozoospermia (MONDO:0850098), plasma cell myeloma (MONDO:0009693), intellectual disability (MONDO:0001071), syndromic intellectual disability (MONDO:0000508), spermatogenic failure (MONDO:0004983), congenital anomaly of kidney and urinary tract (MONDO:0019719)

Orphanet (3): Multiple myeloma (Orphanet:29073), AL amyloidosis (Orphanet:85443), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

28 total (28 of 28 shown, HPO-id order):

HPO	Term
HP:0000276	Long face
HP:0000280	Coarse facial features
HP:0000316	Hypertelorism
HP:0000348	High forehead
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000577	Exotropia
HP:0000718	Aggressive behavior
HP:0000729	Autistic behavior
HP:0000733	Motor stereotypy
HP:0000750	Delayed speech and language development
HP:0000767	Pectus excavatum
HP:0001182	Tapered finger
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001419	X-linked recessive inheritance
HP:0002136	Broad-based gait
HP:0002194	Delayed gross motor development
HP:0002307	Drooling
HP:0003593	Infantile onset
HP:0007018	Attention deficit hyperactivity disorder
HP:0008070	Sparse hair
HP:0010864	Severe intellectual disability
HP:0012810	Wide nasal base
HP:0100710	Impulsivity
HP:0100807	Long fingers

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001713_17	Dental caries	3.000000e-06
GCST002127_10	Periodontitis (Mean PAL)	5.000000e-06
GCST90000047_271	Age at first sexual intercourse	4.000000e-11
GCST90002383_123	Hematocrit	4.000000e-09
GCST90002398_36	Neutrophil count	3.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009749	age at first sexual intercourse measurement
EFO:0004348	hematocrit
EFO:0004833	neutrophil count

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009101	Multiple Myeloma	C04.557.595.500; C14.907.454.460; C15.378.147.780.650; C15.378.463.515.460; C20.683.515.845; C20.683.780.650
D065886	Neurodevelopmental Disorders	F03.625
C566906	Cakut (supp.)

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
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation, increases mutagenesis	3
Cadmium Chloride	increases abundance, increases expression, decreases expression	2
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	decreases expression	1
FR900359	decreases phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
testosterone enanthate	affects expression	1
sodium arsenite	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
coumarin	affects phosphorylation	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
(+)-JQ1 compound	increases expression	1
Sunitinib	decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Atrazine	increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Cadmium	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Cannabidiol	increases expression	1
Hydrogen Peroxide	affects expression	1
Lead	affects splicing	1
Manganese	decreases expression, increases abundance	1
Niclosamide	increases expression	1
Dronabinol	increases expression	1
Tretinoin	decreases expression	1
Urethane	increases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	increases expression	1

Cellosaurus cell lines

7 cell lines: 7 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0098	SKM-1	Cancer cell line	Male
CVCL_1071	AML-193	Cancer cell line	Female
CVCL_1432	MUTZ-2	Cancer cell line	Male
CVCL_1620	OCI-AML-5	Cancer cell line	Male
CVCL_8441	SR-91	Cancer cell line	Female
CVCL_A2CR	A375-R1	Cancer cell line	Female
CVCL_IM24	SKM-1/HHT	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00104104	PHASE4	COMPLETED	A Multiple Myeloma Trial in Patients With Bone Metastases
NCT00211211	PHASE4	COMPLETED	FREE Study - Fracture Reduction Evaluation
NCT00242528	PHASE4	WITHDRAWN	Open-label Study, to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Bone Lesions Secondary to Multiple Myeloma.
NCT00257114	PHASE4	COMPLETED	Evaluation of VELCADE Given as Retreatment to Multiple Myeloma Patients for Efficacy, Safety and Tolerability
NCT00352703	PHASE4	COMPLETED	PROMPT - Palifermin in Reduction of Oral Mucositis in PBSC Transplantation
NCT00361140	PHASE4	COMPLETED	Busulfan Safety/Efficacy as Conditioning Prior to Hematopoietic Cell Transplantation (HCT)
NCT00622505	PHASE4	COMPLETED	Zoledronic Acid Treatment (Every 4 or 12 Weeks) to Prevent Skeletal Complications in Advanced Multiple Myeloma Participants
NCT00652041	PHASE4	COMPLETED	Bortezomib/Adriamycine/Melfalan/Prednisone (VAMP)/Thalidomide/Cyclophosphamide/Dexamethasone (TaCyDex) or Bortezomib/Melfalan/Prednisone (V-MP)/TaCyDex) in Refractary or Relapsed Multiple Myeloma
NCT00733538	PHASE4	COMPLETED	Stage I Multiple Myeloma Treatment
NCT01087008	PHASE4	COMPLETED	Zoledronic Acid in Patients With Multiple Myeloma and Asymptomatic Biochemical Relapse
NCT01249690	PHASE4	UNKNOWN	Efficacy Study of PAD and TAD in Newly Diagnosed Multiple Myeloma
NCT01410929	PHASE4	WITHDRAWN	Evaluation of Vertebral Compression Fracture Fixation With RF Kyphoplasty in Patients With Multiple Myeloma
NCT01731886	PHASE4	COMPLETED	Lenalidomide and Dexamethasone With/Without Stem Cell Transplant in Patients With Multiple Myeloma
NCT01868828	PHASE4	UNKNOWN	A Study of PAD Versus Velcade, Cyclophosphamide and Dexamethasone (VCD) Treatment in Subjects With Multiple Myeloma
NCT02268890	PHASE4	COMPLETED	A Pharmacokinetic Study of Bortezomib in Taiwanese Participants With Multiple Myeloma
NCT02286830	PHASE4	COMPLETED	Prolonged Protection From Bone Disease in Multiple Myeloma
NCT02559154	PHASE4	UNKNOWN	Modified Bortezomib-based Combination Therapy for Multiple Myeloma
NCT02577783	PHASE4	UNKNOWN	PDD vs PAD to Treat Initially Diagnosed MM
NCT02773550	PHASE4	TERMINATED	Treatment With a Scheme With Low Doses of Bortezomib / Melphalan / Prednisone (MPV) in Patients With Multiple Myeloma
NCT02958969	PHASE4	COMPLETED	Apixaban for Primary Prevention of Venous Thromboembolism in Patients With Multiple Myeloma
NCT03173092	PHASE4	TERMINATED	A Study of Ixazomib (NINLARO®) in Combination With Lenalidomide and Dexamethasone (IRD) for the Treatment of Participants With Multiple Myeloma (MM)
NCT03619252	PHASE4	COMPLETED	Pneumococcal Vaccination of Multiple Myeloma Patients on Novel Agents
NCT03768960	PHASE4	COMPLETED	A Study of DARZALEX (Daratumumab) In Indian Participants With Relapsed and Refractory Multiple Myeloma, Whose Prior Therapy Included a Proteasome Inhibitor and an Immunomodulatory Agent
NCT03829371	PHASE4	ACTIVE_NOT_RECRUITING	STUDY COMPARING TWO STANDARD TREATMENTS IN AUTOLOGOUS STEM CELL TRANSPLANTATION INELIGIBLE POPULATION AFFECTED BY MULTIPLE MYELOMA
NCT03908138	PHASE4	UNKNOWN	RDD Versus VDD in Newly Diagnosed Patients With Multiple Myeloma
NCT04217967	PHASE4	COMPLETED	Ixazomib, Lenalidomide, and Combination for Maintenance in NDMM Patients
NCT04952766	PHASE4	COMPLETED	Study Evaluating SARS-CoV-2 (COVID-19) Humoral Response After BNT162b2 Vaccine in Immunocompromised Adults Compared to Healthy Adults
NCT04989140	PHASE4	UNKNOWN	Study of Pomalidomide, Oral Dexamethasone and Ixazomib in Patients With Relapsed MM Who Have Received Lenalidomide
NCT05183139	PHASE4	WITHDRAWN	A Multicenter In-class Transition Study of Ixazomib Combined With Pomalidomide and Dexamethasone or With Lenalidomide and Dexamethasone in Adults With Relapsed/Refractory Multiple Myeloma
NCT05201781	PHASE4	RECRUITING	A Long-term Study for Participants Previously Treated With Ciltacabtagene Autoleucel
NCT05429515	PHASE4	NOT_YET_RECRUITING	Effect of HFR-SUPRA in the Treatment of Multiple Myeloma-related Acute Kidney Injury
NCT05511428	PHASE4	COMPLETED	Home Based Daratumumab Administration for Patients With Multiple Myeloma
NCT05545202	PHASE4	UNKNOWN	A Randomized, Comparative, Double-blind Trial of Pentaisomaltose and Dimethyl Sulphoxide for Cryoprotection of Hematopoietic Stem Cells in Subjects With Multiple Myeloma or Malignant Lymphoma With a Need for Autologous Transplantation
NCT05555329	PHASE4	COMPLETED	Alternative Dosing Scheme of Pomalidomide 4 mg Every Other Day Versus Pomalidomide 2 mg and 4 mg Every Day; the POMAlternative Study
NCT05722405	PHASE4	RECRUITING	Ixazomib Plus Low-dose Lenalidomide Versus Ixazomib Alone for Maintenance Treatment of High Risk Multiple Myeloma
NCT05855122	PHASE4	UNKNOWN	Safety and ASCT-related Symptom Burden Optimization of Tocilizumab in ASCT Following HD Melphalan Conditioning for Multiple Myeloma Patients
NCT05944783	PHASE4	NOT_YET_RECRUITING	Bioequivalence Studies of Dasatinib 100 Mg