BCAS3

Summary

BCAS3 (BCAS3 microtubule associated cell migration factor, HGNC:14347) is a protein-coding gene on chromosome 17q23.2, encoding BCAS3 microtubule associated cell migration factor (Q9H6U6). Plays a role in angiogenesis.

Enables several functions, including acetyltransferase activator activity; beta-tubulin binding activity; and histone acetyltransferase binding activity. Involved in cellular response to estrogen stimulus; positive regulation of catalytic activity; and positive regulation of transcription by RNA polymerase II. Located in euchromatin; nucleus; and phagophore assembly site. Implicated in Hengel-Maroofian-Schols syndrome. Biomarker of breast cancer.

Source: NCBI Gene 54828 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Hengel-Maroofian-Schols syndrome (Strong, GenCC)
• GWAS associations: 114
• Clinical variants (ClinVar): 185 total — 2 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 39
• MANE Select transcript: NM_017679

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14347
Approved symbol	BCAS3
Name	BCAS3 microtubule associated cell migration factor
Location	17q23.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20128, PHAF2
Ensembl gene	ENSG00000141376
Ensembl biotype	protein_coding
OMIM	607470
Entrez	54828

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 13 protein_coding, 13 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay, 3 retained_intron

ENST00000390652, ENST00000407086, ENST00000408905, ENST00000585744, ENST00000585812, ENST00000585979, ENST00000586041, ENST00000586241, ENST00000586484, ENST00000586705, ENST00000587002, ENST00000587037, ENST00000587294, ENST00000587872, ENST00000588008, ENST00000588168, ENST00000588462, ENST00000588532, ENST00000588569, ENST00000588720, ENST00000588874, ENST00000589222, ENST00000589916, ENST00000590128, ENST00000590352, ENST00000591147, ENST00000591371, ENST00000592393, ENST00000592702, ENST00000592827, ENST00000592848, ENST00000593004, ENST00000626960

RefSeq mRNA: 8 — MANE Select: NM_017679 NM_001099432, NM_001320470, NM_001330413, NM_001330414, NM_001353144, NM_001353145, NM_001353146, NM_017679

CCDS: CCDS11626, CCDS45749, CCDS82176, CCDS82177, CCDS82178

Canonical transcript exons

ENST00000407086 — 24 exons

Exon	Start	End
ENSE00002766277	60677851	60677914
ENSE00003461111	60808004	60808076
ENSE00003478290	61015751	61015901
ENSE00003489219	61034666	61034790
ENSE00003525098	60683982	60684036
ENSE00003539906	61040792	61040892
ENSE00003551834	61084467	61084564
ENSE00003560507	61391977	61392831
ENSE00003564419	60889695	60889771
ENSE00003565063	60689686	60689761
ENSE00003570000	60902620	60902703
ENSE00003573829	61078333	61078529
ENSE00003578929	60868576	60868683
ENSE00003613162	60910532	60910702
ENSE00003624722	61368327	61368494
ENSE00003639021	60747198	60747279
ENSE00003643191	60709219	60709325
ENSE00003657120	61074920	61075020
ENSE00003661471	60924407	60924500
ENSE00003669605	60874662	60874738
ENSE00003681140	60989971	60990235
ENSE00003692889	61037889	61038054
ENSE00003693165	60679453	60679540
ENSE00003790310	60947219	60947352

Expression profiles

Bgee: expression breadth ubiquitous, 214 present calls, max score 94.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.8392 / max 301.4259, expressed in 1785 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
162056	16.2335	1783
162055	0.3658	195
162064	0.1311	56
162072	0.0992	39
162059	0.0097	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	94.37	gold quality
sural nerve	UBERON:0015488	93.72	gold quality
right uterine tube	UBERON:0001302	91.52	gold quality
bone marrow cell	CL:0002092	89.46	gold quality
calcaneal tendon	UBERON:0003701	89.23	gold quality
prefrontal cortex	UBERON:0000451	88.84	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.76	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.75	gold quality
right coronary artery	UBERON:0001625	88.69	gold quality
cortical plate	UBERON:0005343	88.38	gold quality
popliteal artery	UBERON:0002250	87.68	gold quality
tibial artery	UBERON:0007610	87.66	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.60	gold quality
frontal cortex	UBERON:0001870	86.75	gold quality
right frontal lobe	UBERON:0002810	86.75	gold quality
corpus callosum	UBERON:0002336	86.71	gold quality
aorta	UBERON:0000947	86.49	gold quality
muscle of leg	UBERON:0001383	86.24	gold quality
neocortex	UBERON:0001950	86.04	gold quality
gastrocnemius	UBERON:0001388	86.01	gold quality
left coronary artery	UBERON:0001626	85.82	gold quality
ganglionic eminence	UBERON:0004023	85.60	gold quality
epithelium of bronchus	UBERON:0002031	85.50	gold quality
right lung	UBERON:0002167	85.49	gold quality
coronary artery	UBERON:0001621	85.34	gold quality
ascending aorta	UBERON:0001496	85.16	gold quality
adrenal tissue	UBERON:0018303	85.14	gold quality
thoracic aorta	UBERON:0001515	85.13	gold quality
Brodmann (1909) area 9	UBERON:0013540	85.03	gold quality
bronchus	UBERON:0002185	84.96	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.08

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EHMT2, ESR1, GATA3, MTA1, MTA3

miRNA regulators (miRDB)

27 targeting BCAS3, 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-12118	100.00	65.88	1270
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-4520-2-3P	99.14	69.28	1009
HSA-MIR-10526-3P	97.86	64.97	1342
HSA-MIR-4700-3P	97.74	68.64	1014
HSA-MIR-27A-5P	97.01	65.63	528
HSA-MIR-873-3P	96.84	66.09	786
HSA-MIR-6085	96.57	64.11	621
HSA-MIR-644A	96.02	66.52	786
HSA-MIR-6753-5P	94.70	64.08	470
HSA-MIR-6813-5P	94.68	64.20	588

Literature-anchored findings (GeneRIF, showing 12)

• role for MTA1-BCAS3 pathway in promoting cancerous phenotypes in breast tumor cells (PMID:16617102)
• BCAS3 overexpression in hormone receptor-positive premenopausal breast cancer seemed to be associated with impaired responses to tamoxifen (PMID:16855396)
• Physically associated with histone H3 and histone acetyltransferase complex protein P/CAF (p300/CBP-associated factor) and possesses histone acetyltransferase activity. (PMID:17505058)
• BCAS3 is mis-expressed in brain tumors and could serve as a human ES cell and tumor marker (PMID:18030336)
• Real-time PCR validated that up-regulation of sulphiredoxin 1 homolog (SRXN1), hemeoxygenase 1 (HMOX1), and breast carcinoma amplified sequence 3 (BCAS3) were consistently modulated. (PMID:21742584)
• BCAS3 single nucleotide polymorphism is associated with gout. (PMID:29879923)
• This study identifies the novel and essential role of Rudhira in cytoskeletal cross-talk and assigns function to the conserved BCAS3 domain. (PMID:30995157)
• Mammalian BCAS3 and C16orf70 associate with the phagophore assembly site in response to selective and non-selective autophagy. (PMID:33499712)
• Bi-allelic loss-of-function variants in BCAS3 cause a syndromic neurodevelopmental disorder. (PMID:34022130)
• Polymorphism in the GATM Locus Associated with Dialysis-Independent Chronic Kidney Disease but Not Dialysis-Dependent Kidney Failure. (PMID:34071541)
• BCAS3 exhibits oncogenic properties by promoting CRL4A-mediated ubiquitination of p53 in breast cancer. (PMID:34240781)
• BCAS3 accelerates glioblastoma tumorigenesis by restraining the P53/GADD45alpha signaling pathway. (PMID:35659972)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	bcas3	ENSDARG00000090764
mus_musculus	Bcas3	ENSMUSG00000059439
rattus_norvegicus	Bcas3	ENSRNOG00000066893
drosophila_melanogaster	rudhira	FBGN0266019
caenorhabditis_elegans		WBGENE00018953

Protein

Protein identifiers

BCAS3 microtubule associated cell migration factor — Q9H6U6 (reviewed: Q9H6U6)

Alternative names: Breast carcinoma-amplified sequence 3, GAOB1

All UniProt accessions (10): Q9H6U6, K7EIE2, K7EIR7, K7EJH7, K7EJU7, K7EKB0, K7ELH0, K7EML5, K7EQA6, K7ESE9

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in angiogenesis. Participates in the regulation of cell polarity and directional endothelial cell migration by mediating both the activation and recruitment of CDC42 and the reorganization of the actin cytoskeleton at the cell leading edge. Promotes filipodia formation. Functions synergistically with PELP1 as a transcriptional coactivator of estrogen receptor-responsive genes. Stimulates histone acetyltransferase activity. Binds to chromatin. Plays a regulatory role in autophagic activity. In complex with PHAF1, associates with the preautophagosomal structure during both non-selective and selective autophagy. Probably binds phosphatidylinositol 3-phosphate (PtdIns3P) which would mediate the recruitment preautophagosomal structures.

Subunit / interactions. Interacts with histone H3, ESR1, KAT2B and PELP1; the interactions occur in a estrogen-dependent manner. Interacts with beta-tubulin and VIM. Interacts (via C-terminal) with PHAF1; the interaction is requrired for the association with the phagophore.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Preautophagosomal structure.

Tissue specificity. Expressed in stomach, liver, lung, kidney, prostate, testis, thyroid gland, adrenal gland, brain, heart, skeletal muscle, colon, spleen, small intestine, placenta, blood leukocyte and mammary epithelial cells. Expressed in undifferentiated ES cells. Expressed in blood islands and nascent blood vessels derived from differentiated ES cells into embryoid bodies (BD). Expressed in endothelial cells. Not detected in brain. Expressed in brain tumors (at protein level). Expressed in brain. Highly expressed in breast cancers and in glioma cell lines.

Disease relevance. A chromosomal aberration involving BCAS3 has been found in some breast carcinoma cell lines. Translocation t(17;20)(q23;q13) with BCAS4. Hengel-Maroofian-Schols syndrome (HEMARS) [MIM:619641] An autosomal recessive disorder characterized by severe global developmental delay apparent from infancy or early childhood. Affected individuals have delayed walking or inability to walk, impaired intellectual development with poor or absent speech, lower limb spasticity, poor overall growth, and dysmorphic facial features. Some patients develop seizures. Brain imaging shows thinning of the posterior part of the corpus callosum, delayed myelination, and cerebral and cerebellar atrophy. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Has been proposed to contain 7 WD repeats. This prediction could not be reproduced.

Induction. By estrogen.

Similarity. Belongs to the BCAS3 family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q9H6U6-1	2	yes
Q9H6U6-2	1
Q9H6U6-3	3
Q9H6U6-8	4
Q9H6U6-7	5, Maaab1
Q9H6U6-6	6, Maaab2

RefSeq proteins (8): NP_001092902, NP_001307399, NP_001317342, NP_001317343, NP_001340073, NP_001340074, NP_001340075, NP_060149* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR022175	BCAS3_dom	Domain
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR045142	BCAS3-like	Family
IPR048382	BCAS3_WD40	Domain

Pfam: PF12490, PF21034

UniProt features (52 total): sequence variant 10, mutagenesis site 9, sequence conflict 8, modified residue 7, region of interest 5, compositionally biased region 4, splice variant 4, cross-link 2, chain 1, repeat 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H6U6-F1	65.25	0.31

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): 824–825 (breakpoint for translocation to form bcas4-bcas3)

Post-translational modifications (9): 1, 461, 480, 488, 838, 886, 898, 215, 215

Mutagenesis-validated functional residues (9):

Position	Phenotype
350	no effect on recruitment to preautophagosomal structure in response to mitophagy. no effect on interaction with phaf1.
370	decreases recruitment to preautophagosomal structure in response to mitophagy. no effect on interaction with phaf1.
372	no effect on recruitment to preautophagosomal structure in response to mitophagy. no effect on interaction with phaf1.
377	no effect on recruitment to preautophagosomal structure in response to mitophagy. no effect on interaction with phaf1.
400	decreases recruitment to preautophagosomal structure in response to mitophagy. no effect on interaction with phaf1.
401	almost abolishes recruitment to preautophagosomal structure in response to mitophagy. no effect on interaction with phaf
426	decreases recruitment to preautophagosomal structure in response to mitophagy. no effect on interaction with phaf1.
428	almost abolishes recruitment to preautophagosomal structure in response to mitophagy. no effect on interaction with phaf
430	almost abolishes recruitment to preautophagosomal structure in response to mitophagy. no effect on interaction with phaf

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (10): angiogenesis (GO:0001525), autophagy (GO:0006914), cell-cell signaling (GO:0007267), positive regulation of endothelial cell migration (GO:0010595), regulation of actin cytoskeleton organization (GO:0032956), response to starvation (GO:0042594), positive regulation of catalytic activity (GO:0043085), response to estrogen (GO:0043627), positive regulation of transcription by RNA polymerase II (GO:0045944), cellular response to estrogen stimulus (GO:0071391)

GO Molecular Function (8): chromatin binding (GO:0003682), acetyltransferase activator activity (GO:0010698), nuclear receptor binding (GO:0016922), histone acetyltransferase binding (GO:0035035), phosphatidylinositol binding (GO:0035091), histone binding (GO:0042393), beta-tubulin binding (GO:0048487), protein binding (GO:0005515)

GO Cellular Component (8): phagophore assembly site (GO:0000407), euchromatin (GO:0000791), nucleus (GO:0005634), cytoplasm (GO:0005737), cytoplasmic microtubule (GO:0005881), cell leading edge (GO:0031252), intermediate filament cytoskeleton (GO:0045111), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
binding	2
cytoplasm	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
cell communication	1
signaling	1
regulation of endothelial cell migration	1
positive regulation of cell migration	1
endothelial cell migration	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
response to stress	1
response to nutrient levels	1
catalytic activity	1
positive regulation of molecular function	1
regulation of catalytic activity	1
response to hormone	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
cellular response to hormone stimulus	1
response to estrogen	1
enzyme activator activity	1
acetyltransferase activity	1
RNA polymerase II-specific DNA-binding transcription factor binding	1
enzyme binding	1
anion binding	1
protein binding	1
tubulin binding	1
chromatin	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
microtubule	1
cytoskeleton	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1126 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BCAS3	BCAS4	Q8TDM0	984
BCAS3	MTA1	Q13330	704
BCAS3	TBX4	P57082	697
BCAS3	TBX2	Q13207	628
BCAS3	PHAF1	Q9BSU1	614
BCAS3	APPBP2	Q92624	517
BCAS3	ESR1	P03372	512
BCAS3	PLEKHG1	Q9ULL1	509
BCAS3	CHD4	Q14839	491
BCAS3	USP32	Q8NFA0	479
BCAS3	SLC2A9	Q9NRM0	476
BCAS3	SLC23A3	Q6PIS1	462
BCAS3	AXDND1	Q5T1B0	460
BCAS3	CHCT1	Q86WR6	456
BCAS3	WIPF2	Q8TF74	451

IntAct

63 interactions, top by confidence:

A	B	Type	Score
MAGEE1	MCC	psi-mi:“MI:0914”(association)	0.670
BCAS3	PHAF1	psi-mi:“MI:0915”(physical association)	0.660
WIPI2	BNIP3L	psi-mi:“MI:0914”(association)	0.640
CTBP1	BCAS3	psi-mi:“MI:0915”(physical association)	0.560
CTBP2	BCAS3	psi-mi:“MI:0915”(physical association)	0.560
BCAS3	CDC23	psi-mi:“MI:0915”(physical association)	0.560
BCAS3	CTBP1	psi-mi:“MI:0915”(physical association)	0.560
BCAS3	CTBP2	psi-mi:“MI:0915”(physical association)	0.560
CDC23	BCAS3	psi-mi:“MI:0915”(physical association)	0.560
BCAS3	PLEKHF2	psi-mi:“MI:0915”(physical association)	0.560
BCAS3	VIM	psi-mi:“MI:0403”(colocalization)	0.560
VIM	BCAS3	psi-mi:“MI:0915”(physical association)	0.560
POLR3H	POLR3A	psi-mi:“MI:0914”(association)	0.530
CELA2B	AURKA	psi-mi:“MI:0914”(association)	0.530
MMP26	SLC25A20	psi-mi:“MI:0914”(association)	0.530
PHAF1	PSMG1	psi-mi:“MI:0914”(association)	0.530
WIPI2	PHAF1	psi-mi:“MI:0914”(association)	0.530
ATM	BCAS3	psi-mi:“MI:0915”(physical association)	0.370
BAG4	BCAS3	psi-mi:“MI:0915”(physical association)	0.370
CCND1	BCAS3	psi-mi:“MI:0915”(physical association)	0.370
FBXW7	BCAS3	psi-mi:“MI:0915”(physical association)	0.370
BCAS3	KRAS	psi-mi:“MI:0915”(physical association)	0.370
BCAS3	PALB2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (110): BCAS3 (Two-hybrid), BCAS3 (Two-hybrid), BCAS3 (Two-hybrid), C16orf70 (Two-hybrid), BCAS3 (Two-hybrid), ESR1 (Reconstituted Complex), BCAS3 (Reconstituted Complex), ESR1 (Affinity Capture-Western), BCAS3 (Affinity Capture-Western), PELP1 (Affinity Capture-Western), BCAS3 (Affinity Capture-Western), PELP1 (Reconstituted Complex), BCAS3 (Reconstituted Complex), BCAS3 (Reconstituted Complex), BCAS3 (Far Western)

ESM2 similar proteins: A2AFR3, A2AHJ4, A2RT67, E1C3P4, F1LXF1, F1R7R1, O08873, O42611, O94967, P15056, P28028, P34908, P48553, P51593, Q04982, Q15542, Q3TLI0, Q3UHE1, Q3UVG3, Q5I0B9, Q5XPI4, Q641K1, Q658Y4, Q6DRP4, Q6PAJ1, Q6RI45, Q6TEP1, Q7TMY8, Q7Z6Z7, Q8C092, Q8C735, Q8CCN5, Q8CGF6, Q8CID0, Q8K2Y9, Q8NHY2, Q8QFR2, Q8VDD9, Q8VI24, Q8WWQ0

Diamond homologs: A1CBB8, A1DE24, A2RAG5, A3GFE3, A5DHI9, A5DVU7, A6QTX7, A6SJ85, A6ZWF0, A7A258, A7EW77, A7KAM8, A7TPY4, A7TTC8, I1RKA1, P0CS28, P0CS29, P43601, Q02887, Q0CW30, Q0U2J8, Q1DKJ3, Q2GV40, Q2U6D5, Q4P4N1, Q4WVD0, Q524W4, Q54NA2, Q59P11, Q5ABA6, Q5B464, Q5BH53, Q5MNZ9, Q5QA94, Q5QJC0, Q5ZHN3, Q6AY57, Q6BIA1, Q6BIL4, Q6C044

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 73 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
Anchoring of the basal body to the plasma membrane	5	11.1×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	12
Uncertain significance	129
Likely benign	11
Benign	2

Top pathogenic / likely-pathogenic (14)

Variant ID	HGVS	Classification
1687612	NM_017679.5(BCAS3):c.1906C>T (p.Arg636Ter)	Pathogenic
57501	GRCh37/hg19 17q23(chr17:58934659-60395826)x1	Pathogenic
1048567	NM_017679.5(BCAS3):c.337C>T (p.Gln113Ter)	Likely pathogenic
1048568	NM_017679.5(BCAS3):c.576C>A (p.Cys192Ter)	Likely pathogenic
2664164	NM_017679.5(BCAS3):c.386T>A (p.Leu129Ter)	Likely pathogenic
3256232	NM_017679.5(BCAS3):c.2425G>T (p.Gly809Cys)	Likely pathogenic
3376507	NM_017679.5(BCAS3):c.1630C>T (p.Arg544Ter)	Likely pathogenic
564457	GRCh37/hg19 17q23.2(chr17:58388728-60486746)x1	Likely pathogenic
993272	NM_017679.5(BCAS3):c.2182C>T (p.Gln728Ter)	Likely pathogenic
993273	NM_017679.5(BCAS3):c.1133del (p.Val378fs)	Likely pathogenic
993274	NM_017679.5(BCAS3):c.530del (p.Met177fs)	Likely pathogenic
993275	NC_000017.11:g.60921178_61232194del	Likely pathogenic
993276	NM_017679.5(BCAS3):c.2029+4_2029+7del	Likely pathogenic
993277	NM_017679.5(BCAS3):c.2425G>C (p.Gly809Arg)	Likely pathogenic

SpliceAI

6758 predictions. Top by Δscore:

Variant	Effect	Δscore
17:60679444:T:TA	acceptor_gain	1.0000
17:60679541:G:GG	donor_gain	1.0000
17:60683970:A:AG	acceptor_gain	1.0000
17:60683971:C:G	acceptor_gain	1.0000
17:60684037:GTAA:G	donor_loss	1.0000
17:60684038:T:G	donor_loss	1.0000
17:60689683:CAG:C	acceptor_loss	1.0000
17:60689684:A:AC	acceptor_loss	1.0000
17:60689685:G:GT	acceptor_loss	1.0000
17:60709212:A:AG	acceptor_gain	1.0000
17:60709326:G:GG	donor_gain	1.0000
17:60747192:A:AG	acceptor_gain	1.0000
17:60747193:T:G	acceptor_gain	1.0000
17:60747193:T:TA	acceptor_gain	1.0000
17:60747196:A:AG	acceptor_gain	1.0000
17:60747196:AGATC:A	acceptor_loss	1.0000
17:60747197:G:GA	acceptor_gain	1.0000
17:60747197:GA:G	acceptor_gain	1.0000
17:60747197:GAT:G	acceptor_gain	1.0000
17:60747197:GATC:G	acceptor_gain	1.0000
17:60747197:GATCA:G	acceptor_gain	1.0000
17:60747275:GTTTG:G	donor_gain	1.0000
17:60747280:G:GG	donor_gain	1.0000
17:60868570:TTTTA:T	acceptor_gain	1.0000
17:60868571:TTTAG:T	acceptor_gain	1.0000
17:60868572:TTA:T	acceptor_gain	1.0000
17:60868573:TAG:T	acceptor_gain	1.0000
17:60868574:A:AG	acceptor_gain	1.0000
17:60868574:AGCAC:A	acceptor_gain	1.0000
17:60868575:G:C	acceptor_gain	1.0000

AlphaMissense

5986 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:60684005:T:A	V36D	1.000
17:60684014:T:C	F39S	1.000
17:60709314:T:A	W104R	1.000
17:60709314:T:C	W104R	1.000
17:60874733:T:A	V219D	1.000
17:60889755:C:A	A241D	1.000
17:60902687:T:A	V269D	1.000
17:60902695:G:C	A272P	1.000
17:60902696:C:A	A272D	1.000
17:60902699:C:A	A273D	1.000
17:60947333:G:C	R401T	1.000
17:60947333:G:T	R401M	1.000
17:60947334:G:C	R401S	1.000
17:60947334:G:T	R401S	1.000
17:60947336:G:A	G402E	1.000
17:60990004:T:A	W419R	1.000
17:60990004:T:C	W419R	1.000
17:60990041:T:A	V431D	1.000
17:60990121:T:C	F458L	1.000
17:60990122:T:C	F458S	1.000
17:60990122:T:G	F458C	1.000
17:60990123:C:A	F458L	1.000
17:60990123:C:G	F458L	1.000
17:60990134:C:A	A462D	1.000
17:61038041:T:A	W654R	1.000
17:61038041:T:C	W654R	1.000
17:61075009:T:A	W722R	1.000
17:61075009:T:C	W722R	1.000
17:61075011:G:C	W722C	1.000
17:61075011:G:T	W722C	1.000

dbSNP variants (sampled 300 via entrez): RS1000005545 (17:60981484 T>C), RS1000005958 (17:61175317 G>A), RS1000008331 (17:60890846 T>C), RS1000013020 (17:60882541 C>G), RS1000014680 (17:60822158 A>G), RS1000015346 (17:60723102 G>A), RS1000018644 (17:60767179 G>A,C), RS1000023990 (17:60810450 G>A,C), RS1000033698 (17:61175688 C>T), RS1000036641 (17:61390486 C>T), RS1000038305 (17:61081737 C>A,T), RS1000040258 (17:60936596 T>A), RS1000045498 (17:61154775 G>A), RS1000046407 (17:61223313 C>A,T), RS1000057051 (17:61376539 T>C)

Disease associations

OMIM: gene MIM:607470 | disease phenotypes: MIM:619641

GenCC curated gene-disease

Disease	Classification	Inheritance
Hengel-Maroofian-Schols syndrome	Strong	Autosomal recessive

Mondo (1): Hengel-Maroofian-Schols syndrome (MONDO:0859208)

Orphanet (1): Global developmental delay-intellectual disability-microcephaly-short stature-brain iron accumulation syndrome (Orphanet:697067)

HPO phenotypes

39 total (30 of 39 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000194	Open mouth
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000431	Wide nasal bridge
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000574	Thick eyebrow
HP:0000639	Nystagmus
HP:0000664	Synophrys
HP:0000687	Widely spaced teeth
HP:0000692	Tooth malposition
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001332	Dystonia
HP:0001344	Absent speech
HP:0001347	Hyperreflexia
HP:0001647	Bicuspid aortic valve
HP:0002059	Cerebral atrophy
HP:0002141	Gait imbalance
HP:0002194	Delayed gross motor development
HP:0002445	Tetraplegia
HP:0002493	Upper motor neuron dysfunction

GWAS associations

114 associations (top):

Study	Trait	p-value
GCST000175_44	Height	6.000000e-08
GCST000649_4	Chronic kidney disease	1.000000e-15
GCST000700_3	Vertical cup-disc ratio	3.000000e-08
GCST001535_10	Immune reponse to smallpox (secreted IL-2)	4.000000e-07
GCST001606_9	Renal function-related traits (sCR)	7.000000e-11
GCST001607_8	Renal function-related traits (eGRFcrea)	5.000000e-11
GCST001610_5	Renal function-related traits (BUN)	2.000000e-09
GCST001762_528	Obesity-related traits	7.000000e-06
GCST001791_4	Urate levels	1.000000e-08
GCST001915_40	Alzheimer’s disease (cognitive decline)	1.000000e-11
GCST002724_15	Airway responsiveness in chronic obstructive pulmonary disease	1.000000e-06
GCST002762_19	Optic cup area	4.000000e-11
GCST002762_4	Optic cup area	2.000000e-12
GCST002909_3	Gout	1.000000e-13
GCST003116_5	Coronary artery disease	2.000000e-08
GCST003117_32	Myocardial infarction	8.000000e-06
GCST003372_59	Glomerular filtration rate (creatinine)	8.000000e-22
GCST003401_20	Glomerular filtration rate in non diabetics (creatinine)	3.000000e-22
GCST003790_14	Glomerular filtration rate	8.000000e-14
GCST003790_7	Glomerular filtration rate	1.000000e-06
GCST003790_8	Glomerular filtration rate	3.000000e-06
GCST004137_28	Optic cup area	1.000000e-13
GCST004137_43	Optic cup area	2.000000e-13
GCST004292_36	Glomerular filtration rate (creatinine)	4.000000e-21
GCST004351_23	Bone ultrasound measurement (broadband ultrasound attenuation)	2.000000e-07
GCST004601_151	Red blood cell count	5.000000e-12
GCST004604_33	Hematocrit	4.000000e-11
GCST004615_115	Hemoglobin concentration	6.000000e-11
GCST004787_67	Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease)	1.000000e-09
GCST005194_139	Coronary artery disease	3.000000e-09

EFO canonical traits (26, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0005188	CCL11 measurement
EFO:0004531	urate measurement
EFO:0006897	airway responsiveness measurement
EFO:0004514	bone quantitative ultrasound measurement
EFO:0004305	erythrocyte count
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0004695	intraocular pressure measurement
EFO:0004838	calcium measurement
EFO:0004761	uric acid measurement
EFO:0009270	heel bone mineral density
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0004713	FEV/FVC ratio
EFO:0004314	forced expiratory volume
EFO:0009928	Diuretic use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0006939	cup-to-disc ratio measurement
EFO:0600003	vitamin C measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007986	reticulocyte count
EFO:0007985	platelet crit
EFO:0004309	platelet count
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	8
Aflatoxin B1	decreases expression, increases methylation, affects expression	6
bisphenol A	decreases expression, decreases methylation, increases expression, affects cotreatment	4
Air Pollutants	decreases expression, affects cotreatment, increases abundance, affects expression	3
Ozone	affects cotreatment, decreases expression, increases abundance, affects expression	3
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	2
Acrolein	decreases expression, increases abundance, affects cotreatment	2
Valproic Acid	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
TAK-243	decreases sumoylation	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	affects cotreatment, increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
coumarin	increases phosphorylation	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	decreases expression	1
bisphenol B	decreases expression	1
bisphenol Z	decreases expression	1
(+)-JQ1 compound	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Caffeine	affects phosphorylation	1
Cisplatin	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1661	ZR-75-30	Cancer cell line	Female

Clinical trials (associated diseases)

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