MFHAS1

Summary

MFHAS1 (multifunctional ROCO family signaling regulator 1, HGNC:16982) is a protein-coding gene on chromosome 8p23.1, encoding Malignant fibrous histiocytoma-amplified sequence 1 (Q9Y4C4). Probable GTP-binding protein.

Identified in a human 8p amplicon, this gene is a potential oncogene whose expression is enhanced in some malignant fibrous histiocytomas (MFH). The primary structure of its product includes an ATP/GTP-binding site, three leucine zipper domains, and a leucine-rich tandem repeat, which are structural or functional elements for interactions among proteins related to the cell cycle, and which suggest that overexpression might be oncogenic with respect to MFH.

Source: NCBI Gene 9258 — RefSeq curated summary.

At a glance

• GWAS associations: 76
• Clinical variants (ClinVar): 239 total
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_004225

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16982
Approved symbol	MFHAS1
Name	multifunctional ROCO family signaling regulator 1
Location	8p23.1
Locus type	gene with protein product
Status	Approved
Aliases	MASL1, LRRC65
Ensembl gene	ENSG00000147324
Ensembl biotype	protein_coding
OMIM	605352
Entrez	9258

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000276282, ENST00000520091, ENST00000520715, ENST00000521881

RefSeq mRNA: 1 — MANE Select: NM_004225 NM_004225

CCDS: CCDS34844

Canonical transcript exons

ENST00000276282 — 3 exons

Exon	Start	End
ENSE00001019493	8890061	8893630
ENSE00001391263	8783354	8786055
ENSE00003528810	8797365	8797491

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 97.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.4159 / max 75.2944, expressed in 1622 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
91753	5.6125	1576
91752	0.8034	499

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
saphenous vein	UBERON:0007318	97.21	gold quality
secondary oocyte	CL:0000655	96.79	gold quality
renal medulla	UBERON:0000362	93.96	gold quality
pylorus	UBERON:0001166	91.76	gold quality
superior surface of tongue	UBERON:0007371	91.05	gold quality
cardia of stomach	UBERON:0001162	91.03	gold quality
pericardium	UBERON:0002407	89.70	gold quality
vena cava	UBERON:0004087	89.47	silver quality
pons	UBERON:0000988	89.32	gold quality
cortical plate	UBERON:0005343	89.24	gold quality
nipple	UBERON:0002030	88.97	gold quality
oocyte	CL:0000023	88.67	gold quality
superior vestibular nucleus	UBERON:0007227	88.60	gold quality
gingiva	UBERON:0001828	87.67	gold quality
gingival epithelium	UBERON:0001949	87.58	gold quality
tongue	UBERON:0001723	87.51	gold quality
mucosa of sigmoid colon	UBERON:0004993	87.13	gold quality
trabecular bone tissue	UBERON:0002483	86.91	gold quality
colonic mucosa	UBERON:0000317	86.76	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.30	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.28	gold quality
caput epididymis	UBERON:0004358	86.16	gold quality
penis	UBERON:0000989	85.98	gold quality
body of tongue	UBERON:0011876	85.94	gold quality
rectum	UBERON:0001052	85.67	gold quality
lower lobe of lung	UBERON:0008949	85.67	gold quality
ganglionic eminence	UBERON:0004023	85.47	gold quality
urethra	UBERON:0000057	85.43	gold quality
cerebellar vermis	UBERON:0004720	85.26	gold quality
superficial temporal artery	UBERON:0001614	85.03	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	19.35
E-ANND-3	yes	3.62
E-MTAB-6075	no	98.77

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

123 targeting MFHAS1, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548N	99.98	71.94	4170
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-96-5P	99.95	72.80	2140
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-12133	99.92	71.82	2006

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 7)

• MASL1, a candidate oncogene found in amplification of 8p23.1, is translocated in an immunoblastic B-cell lymphoma cell line. (PMID:14691450)
• MFHAS1 regulates Toll-like receptor (TLR)-dependent signaling. (PMID:20616063)
• aim of the review is to summarize the existing information on MASL1 and also to compile data that could be linked to MASL1 [review] (PMID:22988871)
• MASL1 expression is upregulated during primary human CD34+ cell erythroid differentiation and is an abundant protein in human red blood cells. (PMID:23327923)
• the results indicate that MFHAS1 suppresses TLR4 signaling pathway through induction of PP2A C subunit cytoplasm translocation and subsequent c-Jun degradation, leading finally to decrease AP-1 activity and cytokines expression. (PMID:28609714)
• MFHAS1 deadened high-glucose induced inflammation by activating AKT/HO-1 pathway (PMID:29168081)
• Silencing MFHAS1 Induces Pyroptosis via the JNK-activated NF-kappaB/Caspase1/ GSDMD Signal Axis in Breast Cancer. (PMID:37936452)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mfhas1	ENSDARG00000079104
mus_musculus	Mfhas1	ENSMUSG00000070056
rattus_norvegicus	Mfhas1	ENSRNOG00000011431

Paralogs (31): LRRC7 (ENSG00000033122), PHLPP2 (ENSG00000040199), LRRC40 (ENSG00000066557), LRCH4 (ENSG00000077454), PHLPP1 (ENSG00000081913), SHOC2 (ENSG00000108061), ERBIN (ENSG00000112851), LRRC39 (ENSG00000122477), LRCH2 (ENSG00000130224), LRCH1 (ENSG00000136141), LRRC8A (ENSG00000136802), LRRC1 (ENSG00000137269), LRRC27 (ENSG00000148814), LRRK1 (ENSG00000154237), LRRC58 (ENSG00000163428), LRRC2 (ENSG00000163827), LRRC18 (ENSG00000165383), LRRC28 (ENSG00000168904), LRRC8E (ENSG00000171017), LRRC8C (ENSG00000171488), LRRC8D (ENSG00000171492), PIDD1 (ENSG00000177595), SCRIB (ENSG00000180900), LRCH3 (ENSG00000186001), LRRIQ4 (ENSG00000188306), LRRC8B (ENSG00000197147), LRRC10 (ENSG00000198812), LRRC10B (ENSG00000204950), LRRC30 (ENSG00000206422), LRRC69 (ENSG00000214954), LRRD1 (ENSG00000240720)

Protein

Protein identifiers

Malignant fibrous histiocytoma-amplified sequence 1 — Q9Y4C4 (reviewed: Q9Y4C4)

Alternative names: Malignant fibrous histiocytoma-amplified sequence with leucine-rich tandem repeats 1

All UniProt accessions (1): Q9Y4C4

UniProt curated annotations — full annotation on UniProt →

Function. Probable GTP-binding protein. Functions in innate immunity and more specifically the inflammatory response as a regulator of the Toll-like receptor TLR2 and TLR4 signaling pathways. Negatively regulates the part of the TLR4 signaling pathway that leads to the activation of the transcription factor AP-1. By retaining the phosphatase complex PP2A into the cytoplasm, prevents the dephosphorylation of the AP-1 subunit JUN which is required for proper activation of the transcription factor. Both inhibits and activates the TLR2-dependent signaling pathway. Positively regulates the TLR2 signaling pathway to activate specifically the downstream p38 and JNK MAP kinases and promote the polarization of macrophages toward the pro-inflammatory M1 phenotype. It may also play a role in the regulation of inflammation induced by high glucose through the PKB/AKT signaling pathway. Also involved in erythrocyte differentiation through activation of the ERK1/ERK2 signaling pathway.

Subunit / interactions. Interacts with RAF1. Interacts with HSPD1. Interacts with PPP2CA; retains PPP2CA into the cytoplasm and excludes it from the nucleus. Interacts with PPP2R2A; the interaction is direct. Interacts with PJA2.

Subcellular location. Cytoplasm.

Tissue specificity. Ubiquitously expressed. Overexpressed in malignant fibrous histiocytomas. Expressed in red blood cells (at protein level).

Post-translational modifications. Ubiquitinated. Ubiquitination by PJA2 does not lead MFHAS1 to proteasomal degradation but positively regulates its function in polarization of macrophages.

Disease relevance. A chromosomal aberration involving MFHAS1 may be a cause of B-cell lymphoma. Translocation t(8;14)(p23.1;q21) with a cryptic exon named ‘14q21 element’. The resulting fusion protein named ‘chimeric MASL1’ is tumorigenic in nude mice.

Induction. Up-regulated during erythroid cells differentiation (at protein level). Up-regulated upon Toll-like receptor TLR2 stimulation. Up-regulated in macrophages upon M. tuberculosis infection. Up-regulated upon sepsis. Up-regulated by glucose.

RefSeq proteins (1): NP_004216* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR020859	ROC	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR050216	LRR_domain-containing	Family

Pfam: PF13855

UniProt features (27 total): repeat 13, mutagenesis site 3, region of interest 2, modified residue 2, sequence variant 2, initiator methionine 1, chain 1, domain 1, site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y4C4-F1	84.62	0.60

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): 1000–1001 (breakpoint for translocation to form chimeric masl1)

Post-translational modifications (2): 2, 601

Mutagenesis-validated functional residues (3):

Position	Phenotype
414–556	dominant negative effect on the erk1/erk2 signaling pathway and epo-induced erythroid differentiation.
443	loss of gtp-binding.
450	dominant negative effect on the erk1/erk2 signaling pathway and epo-induced erythroid differentiation.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 345 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_ERYTHROCYTE_HOMEOSTASIS, GOBP_REGULATION_OF_TOLL_LIKE_RECEPTOR_4_SIGNALING_PATHWAY, GOBP_REGULATION_OF_MACROPHAGE_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_REGULATION_OF_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY, GOBP_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM

GO Biological Process (18): inflammatory response (GO:0006954), erythrocyte differentiation (GO:0030218), regulation of toll-like receptor signaling pathway (GO:0034121), negative regulation of toll-like receptor 2 signaling pathway (GO:0034136), positive regulation of toll-like receptor 2 signaling pathway (GO:0034137), negative regulation of toll-like receptor 4 signaling pathway (GO:0034144), intracellular signal transduction (GO:0035556), regulation of macrophage activation (GO:0043030), innate immune response (GO:0045087), positive regulation of JNK cascade (GO:0046330), negative regulation of inflammatory response (GO:0050728), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), positive regulation of ERK1 and ERK2 cascade (GO:0070374), negative regulation of protein localization to nucleus (GO:1900181), positive regulation of p38MAPK cascade (GO:1900745), immune system process (GO:0002376), defense response (GO:0006952), negative regulation of signal transduction (GO:0009968)

GO Molecular Function (5): GTP binding (GO:0005525), ubiquitin protein ligase binding (GO:0031625), protein phosphatase 2A binding (GO:0051721), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of MAPK cascade	3
negative regulation of immune system process	2
negative regulation of signal transduction	2
toll-like receptor 2 signaling pathway	2
regulation of toll-like receptor 2 signaling pathway	2
intracellular anatomical structure	2
signal transduction	2
defense response	1
myeloid cell differentiation	1
erythrocyte homeostasis	1
toll-like receptor signaling pathway	1
regulation of pattern recognition receptor signaling pathway	1
positive regulation of pattern recognition receptor signaling pathway	1
toll-like receptor 4 signaling pathway	1
regulation of toll-like receptor 4 signaling pathway	1
regulation of leukocyte activation	1
macrophage activation	1
immune response	1
defense response to symbiont	1
JNK cascade	1
regulation of JNK cascade	1
inflammatory response	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
regulation of inflammatory response	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
positive regulation of intracellular signal transduction	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
protein localization to nucleus	1
regulation of protein localization to nucleus	1
negative regulation of protein localization	1
p38MAPK cascade	1
regulation of p38MAPK cascade	1
biological_process	1
response to stress	1
regulation of signal transduction	1
negative regulation of cell communication	1
negative regulation of signaling	1

Protein interactions and networks

STRING

926 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MFHAS1	CLDN23	Q96B33	970
MFHAS1	PPP1R3B	Q86XI6	924
MFHAS1	PJA2	O43164	646
MFHAS1	FAM90A7	A6NKC0	506
MFHAS1	DAPK1	P53355	475
MFHAS1	ITPKB	P27987	472
MFHAS1	XKR6	Q5GH73	446
MFHAS1	STK25	O00506	438
MFHAS1	NEK11	Q8NG66	437
MFHAS1	MSRA	Q9UJ68	419
MFHAS1	KIZ	Q2M2Z5	408
MFHAS1	MAP3K4	Q9Y6R4	401
MFHAS1	LIMK1	P53667	395
MFHAS1	ERI1	Q8IV48	393
MFHAS1	PRAG1	Q86YV5	386

IntAct

103 interactions, top by confidence:

A	B	Type	Score
KIF3A	KIF3C	psi-mi:“MI:0914”(association)	0.730
CEP164	TTBK2	psi-mi:“MI:0914”(association)	0.680
KIFAP3	KIF3C	psi-mi:“MI:0914”(association)	0.640
PGRMC2	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.590
MFHAS1	PGRMC2	psi-mi:“MI:0914”(association)	0.590
HSPD1	MFHAS1	psi-mi:“MI:0914”(association)	0.560
HSPD1	MFHAS1	psi-mi:“MI:0915”(physical association)	0.560
VN1R1	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
TAS2R60	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
CDC42EP3	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
TTC27	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
CETN3	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
AHDC1	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
STUB1	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
PSME3IP1	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
ANKRD13D	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
RHBDD1	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
ESRRG	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
CHGB	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
CBLB	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
CALML3	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
ABLIM1	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
TADA3	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
UBL7	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
TOX2	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
CRTC2	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
GSDMD	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
POLA2	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (110): MFHAS1 (Synthetic Growth Defect), MFHAS1 (Affinity Capture-MS), MFHAS1 (Affinity Capture-MS), MFHAS1 (Affinity Capture-MS), MFHAS1 (Affinity Capture-MS), PJA2 (Affinity Capture-MS), MFHAS1 (Affinity Capture-Western), PJA2 (Affinity Capture-Western), MFHAS1 (Reconstituted Complex), MFHAS1 (Affinity Capture-RNA), VN1R1 (Reconstituted Complex), TAS2R60 (Reconstituted Complex), CDC42EP3 (Reconstituted Complex), TTC27 (Reconstituted Complex), PGRMC2 (Reconstituted Complex)

ESM2 similar proteins: A0A061IR73, A0A1B0GUU1, A6H687, A8MYJ7, B1WC39, D3ZVB0, E1BD59, G3MY25, G3MZC5, O75064, P07199, P27790, P29597, P48988, P52333, P52824, Q08DF2, Q0VCE3, Q13608, Q1JPD6, Q2VPB7, Q3TAP4, Q3U1Y4, Q3ZBE0, Q499M4, Q53EQ6, Q5JZY3, Q62137, Q63272, Q6B0B8, Q6DI92, Q6ZPS2, Q6ZS72, Q7TM95, Q80VI1, Q86UT6, Q8BYG9, Q8N9M5, Q8R5G7, Q8TE96

Diamond homologs: A4IIK1, Q3V1N1, Q9Y4C4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PJA2	“up-regulates activity”	MFHAS1	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	202
Likely benign	19
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

1727 predictions. Top by Δscore:

Variant	Effect	Δscore
8:8797363:A:AC	donor_gain	1.0000
8:8797364:C:CC	donor_gain	1.0000
8:8797487:CTCCC:C	acceptor_gain	1.0000
8:8797488:TCCC:T	acceptor_gain	1.0000
8:8797489:CCC:C	acceptor_gain	1.0000
8:8797489:CCCC:C	acceptor_gain	1.0000
8:8797490:CC:C	acceptor_gain	1.0000
8:8797490:CCCTG:C	acceptor_gain	1.0000
8:8797491:CC:C	acceptor_gain	1.0000
8:8797492:C:CC	acceptor_gain	1.0000
8:8797493:T:A	acceptor_loss	1.0000
8:8797423:G:A	donor_gain	0.9900
8:8797494:G:C	acceptor_gain	0.9900
8:8826865:C:CT	acceptor_gain	0.9900
8:8835359:T:A	donor_gain	0.9900
8:8860068:C:CT	acceptor_gain	0.9900
8:8861058:A:C	donor_gain	0.9900
8:8795204:T:TC	acceptor_gain	0.9800
8:8797192:T:TA	donor_gain	0.9800
8:8797419:A:AC	donor_gain	0.9800
8:8797420:C:CC	donor_gain	0.9800
8:8797494:G:GC	acceptor_gain	0.9800
8:8861037:G:A	donor_gain	0.9800
8:8786052:CTTC:C	acceptor_gain	0.9700
8:8786064:G:GC	acceptor_gain	0.9700
8:8797414:CAT:C	donor_gain	0.9700
8:8797416:T:C	donor_gain	0.9700
8:8797420:CTCG:C	donor_gain	0.9700
8:8823676:C:A	donor_gain	0.9700
8:8866728:A:AC	donor_gain	0.9700

AlphaMissense

6755 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:8797443:C:G	C1016S	1.000
8:8797444:A:G	C1016R	1.000
8:8797444:A:T	C1016S	1.000
8:8890100:A:G	C987R	1.000
8:8890107:A:C	C984W	1.000
8:8890109:A:G	C984R	1.000
8:8890191:C:A	W956C	1.000
8:8890191:C:G	W956C	1.000
8:8890193:A:G	W956R	1.000
8:8890193:A:T	W956R	1.000
8:8891070:C:A	W663C	1.000
8:8891070:C:G	W663C	1.000
8:8891072:A:G	W663R	1.000
8:8891072:A:T	W663R	1.000
8:8891876:A:C	Y395D	1.000
8:8891897:C:A	G388W	1.000
8:8891920:G:T	P380H	1.000
8:8891921:G:A	P380S	1.000
8:8891934:G:C	N375K	1.000
8:8891934:G:T	N375K	1.000
8:8892003:G:C	N352K	1.000
8:8892003:G:T	N352K	1.000
8:8892004:T:A	N352I	1.000
8:8892019:A:G	L347P	1.000
8:8797402:A:C	Y1030D	0.999
8:8797404:A:T	V1029D	0.999
8:8797442:G:C	C1016W	0.999
8:8797443:C:T	C1016Y	0.999
8:8797444:A:C	C1016G	0.999
8:8890066:A:C	F998C	0.999

dbSNP variants (sampled 300 via entrez): RS1000001909 (8:8880038 G>A), RS1000008271 (8:8886028 C>A,T), RS1000013891 (8:8853188 G>A), RS1000079673 (8:8782914 T>A,C,G), RS1000129274 (8:8785635 C>T), RS1000151491 (8:8827048 T>G), RS1000157989 (8:8836294 T>A,C), RS1000158917 (8:8785403 G>T), RS1000174036 (8:8855322 A>T), RS1000188804 (8:8881866 G>A), RS1000237253 (8:8837529 G>C), RS1000239294 (8:8815792 C>A), RS1000239765 (8:8863913 G>A), RS1000252220 (8:8868039 C>G,T), RS1000274273 (8:8841388 T>C,G)

Disease associations

OMIM: gene MIM:605352 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): myoepithelial tumor (MONDO:0002380)

Orphanet (0):

HPO phenotypes

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

GWAS associations

76 associations (top):

Study	Trait	p-value
GCST000245_5	Conduct disorder (maternal expressed emotions interaction)	6.000000e-06
GCST002481_5	Acne (severe)	9.000000e-07
GCST004351_13	Bone ultrasound measurement (broadband ultrasound attenuation)	4.000000e-07
GCST004574_11	Skin aging (microtopography measurement)	8.000000e-06
GCST005232_114	Neuroticism	2.000000e-29
GCST005232_129	Neuroticism	3.000000e-31
GCST005237_1	Mood instability	5.000000e-09
GCST005238_1	Mood instability	2.000000e-09
GCST005752_183	Systemic lupus erythematosus	3.000000e-07
GCST006190_33	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	2.000000e-11
GCST006190_44	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	5.000000e-06
GCST006190_91	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	4.000000e-11
GCST006192_20	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	3.000000e-21
GCST006192_31	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	1.000000e-08
GCST006192_6	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	8.000000e-22
GCST006192_65	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	1.000000e-09
GCST006193_17	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	1.000000e-11
GCST006193_27	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	1.000000e-06
GCST006193_57	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	1.000000e-11
GCST006195_26	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	3.000000e-22
GCST006195_47	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	3.000000e-23
GCST006195_57	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	3.000000e-09
GCST006195_8	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	1.000000e-08
GCST007324_46	Adventurousness	4.000000e-08
GCST007325_310	General risk tolerance (MTAG)	3.000000e-14
GCST007335_16	Age at first sexual intercourse	2.000000e-10
GCST007692_122	Chronic obstructive pulmonary disease	4.000000e-10
GCST007709_185	General factor of neuroticism	4.000000e-11
GCST007709_222	General factor of neuroticism	1.000000e-08
GCST007709_31	General factor of neuroticism	1.000000e-18

EFO canonical traits (21, from GWAS)

EFO ID	Trait name
EFO:0008342	parental emotion expression measurmement
EFO:0004514	bone quantitative ultrasound measurement
EFO:0007660	neuroticism measurement
EFO:0008475	mood instability measurement
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0006335	systolic blood pressure
EFO:0008579	risk-taking behaviour
EFO:0009749	age at first sexual intercourse measurement
EFO:0009930	Calcium channel blocker use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0005001	phenylalanine measurement
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement
EFO:0004327	electrocardiography
EFO:0009963	bipolar I disorder
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004736	aspartate aminotransferase measurement
EFO:0004533	alkaline phosphatase measurement
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009208	Myoepithelioma	C04.557.435.585

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	increases expression, affects cotreatment	3
trichostatin A	affects cotreatment, decreases expression	2
Acetaminophen	increases expression	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Nickel	increases expression	2
Valproic Acid	increases expression, increases methylation	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
TL8-506	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	decreases expression	1
cupric chloride	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
eprenetapopt	affects expression, affects reaction	1
bisphenol S	increases methylation	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Amiodarone	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	decreases phosphorylation	1
Estradiol	increases expression	1
Lipopolysaccharides	increases expression, affects response to substance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03600649	PHASE1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT05266196	PHASE1/PHASE2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	PHASE1/PHASE2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06625190	PHASE1/PHASE2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT06244420	Not specified	COMPLETED	Malignant Myoepithelioma of Bone and Soft Tissues: Diagnostic Imaging and Histology in Relation to Prognosis