RASSF6

Summary

RASSF6 (Ras association domain family member 6, HGNC:20796) is a protein-coding gene on chromosome 4q13.3, encoding Ras association domain-containing protein 6 (Q6ZTQ3). Involved in the induction of apoptosis, through both caspase-dependent and caspase-independent pathways.

This gene encodes a member of the Ras-association domain family (RASSF). Members of this family form the core of a highly conserved tumor suppressor network, the Salvador-Warts-Hippo (SWH) pathway. The protein encoded by this gene is a Ras effector protein that induces apoptosis. A genomic region containing this gene has been linked to susceptibility to viral bronchiolitis. Alternative splicing results in multiple transcript variants and protein isoforms.

Source: NCBI Gene 166824 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 79 total
• MANE Select transcript: NM_177532

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20796
Approved symbol	RASSF6
Name	Ras association domain family member 6
Location	4q13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000169435
Ensembl biotype	protein_coding
OMIM	612620
Entrez	166824

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 12 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000307439, ENST00000335049, ENST00000342081, ENST00000395777, ENST00000512591, ENST00000853548, ENST00000853549, ENST00000853550, ENST00000961592, ENST00000961593, ENST00000961594, ENST00000961595, ENST00000961596

RefSeq mRNA: 4 — MANE Select: NM_177532 NM_001270391, NM_001270392, NM_177532, NM_201431

CCDS: CCDS3558, CCDS3559, CCDS58904, CCDS58905

Canonical transcript exons

ENST00000307439 — 11 exons

Exon	Start	End
ENSE00001141376	73576410	73576507
ENSE00001141382	73576613	73576731
ENSE00001141400	73582189	73582290
ENSE00001141414	73587840	73587934
ENSE00001141421	73593451	73593593
ENSE00001141428	73598640	73598718
ENSE00001303840	73585180	73585364
ENSE00001326273	73581817	73581868
ENSE00001813580	73571550	73576310
ENSE00001824671	73620288	73620436
ENSE00003571448	73611731	73611829

Expression profiles

Bgee: expression breadth ubiquitous, 173 present calls, max score 96.70.

FANTOM5 (CAGE): breadth broad, TPM avg 2.5602 / max 217.0566, expressed in 300 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52497	1.5731	238
52496	0.2456	77
52500	0.2404	125
52498	0.2186	77
52499	0.1789	75
52494	0.0408	20
52501	0.0405	13
52495	0.0137	8
52502	0.0087	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	96.70	gold quality
palpebral conjunctiva	UBERON:0001812	95.66	gold quality
ileal mucosa	UBERON:0000331	95.61	gold quality
thymus	UBERON:0002370	95.50	gold quality
epithelial cell of pancreas	CL:0000083	94.39	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.38	gold quality
colonic mucosa	UBERON:0000317	93.87	gold quality
jejunal mucosa	UBERON:0000399	93.73	gold quality
pylorus	UBERON:0001166	92.20	gold quality
epithelium of nasopharynx	UBERON:0001951	89.68	gold quality
bronchial epithelial cell	CL:0002328	88.49	gold quality
duodenum	UBERON:0002114	87.95	gold quality
bronchus	UBERON:0002185	87.81	gold quality
rectum	UBERON:0001052	86.50	gold quality
kidney epithelium	UBERON:0004819	86.04	silver quality
nasal cavity epithelium	UBERON:0005384	84.38	gold quality
cardia of stomach	UBERON:0001162	84.23	gold quality
islet of Langerhans	UBERON:0000006	84.22	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	84.17	gold quality
mucosa of paranasal sinus	UBERON:0005030	83.68	gold quality
nasal cavity mucosa	UBERON:0001826	83.16	gold quality
upper arm skin	UBERON:0004263	83.00	silver quality
pancreas	UBERON:0001264	82.22	gold quality
mucosa of transverse colon	UBERON:0004991	82.07	gold quality
placenta	UBERON:0001987	81.54	gold quality
body of pancreas	UBERON:0001150	81.10	gold quality
epithelium of mammary gland	UBERON:0003244	79.90	gold quality
mammary duct	UBERON:0001765	79.81	gold quality
upper leg skin	UBERON:0004262	78.75	gold quality
oviduct epithelium	UBERON:0004804	78.33	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.62
E-CURD-114	yes	10.29
E-MTAB-8410	yes	3.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

164 targeting RASSF6, 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-1277-5P	100.00	73.95	5056
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-1236-3P	99.94	68.04	1695

Literature-anchored findings (GeneRIF, showing 26)

• These findings indicate that RASSF6 is implicated in apoptosis in HeLa cells and that it triggers both caspase-dependent and caspase-independent pathways. (PMID:17367779)
• Demonstrates properties of a Ras effector and tumor suppressor but exhibits biological properties that are unique and distinct from those of other family members. (PMID:17404571)
• Sequencing revealed RASSF6 and RASSF10 were the only RASSF members with a high frequency of leukaemia-specific methylation. (PMID:19570220)
• activation of MST2 causes apoptosis through the Hippo pathway, as well as through a RASSF6-mediated pathway (PMID:19797269)
• Decreased expression of RASSF6 is associated with gastric cancer. (PMID:21442347)
• The RASSF gene family members RASSF5, RASSF6 and RASSF7 show frequent DNA methylation in neuroblastoma. (PMID:22695170)
• RASSF6-induced apoptosis partially depends on p53. RASSF6 binds MDM2 and facilitates its ubiquitination. RASSF6 depletion blocks the increase of p53 in response to UV exposure and up-regulation of p53 target genes. (PMID:24003224)
• Mechanistic investigation shows that RASSF6 triggers p21(Cip1/Waf1) accumulation to induce G 1 cell cycle arrest and promote apoptosis upon exposure to pro-apoptotic agents, and both of these mechanisms appear to be mediated by activated JNK signaling. (PMID:24626183)
• downregulation of RASSF6 in highly metastatic nasopharyngeal carcinoma cells contributed to their treatment resistance (PMID:25028967)
• RASSF6 exhibits promoter hypermethylation in metastatic melanoma and inhibits invasion in melanoma cells.RASSF6 exhibits the highest frequency of inactivation in melanoma and in melanoma brain metastases. (PMID:25482183)
• RASSF6 expression is an independent biomarker of an unfavorable prognosis in patients with pancreatic ductal adenocarcinoma. (PMID:26074700)
• Results suggest that down-regulation of RASSF2, and RASSF6 is a tumor-specific phenomenon and their inactivation through CpG island methylation may play important roles in gastric cardia carcinogenesis. (PMID:26456015)
• Data suggest that Ras-association domain family protein 6 (RASSF6) may serve as a candidate against tumor growth for sporadic colorectal cancer (sCRC). (PMID:27009808)
• RASSF6 is down-regulated and exhibits tumor suppressor activities in hepatocellular carcinoma. (PMID:27983932)
• Overexpression or silencing of RASSF6 could partially reverse the effects of the overexpression or repression of miR-181a-5p on GC progress caused by activation of the MAKP pathway in vitro and in vivo. (PMID:28043911)
• RASSF6 and RASSF10 were frequently hypermethylated in the samples at the time of diagnosis of adult acute lymphoblastic leukemia patients (PMID:28869817)
• Study reports the interaction of BCL-XL with RASSF6. BCL-XL inhibits the interaction between RASSF6 and MDM2 and suppresses p53 expression. Consequently, BCL-XL antagonizes RASSF6-mediated apoptosis. Thus, the inhibition of RASSF6-mediated apoptosis also underlies the prosurvival role of BCL-XL. (PMID:29193479)
• RASSF6 increases unphosphorylated pRb and augments the interaction between pRb and E2F1. Moreover, RASSF6 induces TP73 target genes via pRb and E2F1 in a p53-negative background. (PMID:29891515)
• RASSF6 functions as a potential tumor suppressor in human breast cancer through activation of Hippo pathway. (PMID:29964010)
• MiR-496 promotes migration and epithelial-mesenchymal transition by targeting RASSF6 in colorectal cancer. (PMID:31273789)
• DNA methylation status of the RASSF6 and RASSF10 genes could be potential biomarkers for the assessment of residual disease in PB of patients with ALL. (PMID:31486880)
• The results indicate that the RASSF6-TRIM16 axis is a key effector in ESCC progression and that RASSF6 serves as a potential target for the treatment of ESCC. (PMID:31812473)
• lncRNA TUSC7 inhibits osteosarcoma progression through the miR181a/RASSF6 axis. (PMID:33416181)
• Down-regulation of circITCH promotes osteosarcoma development and resistance to doxorubicin via the miR-524/RASSF6 axis. (PMID:34151476)
• DNA Damage Triggers the Nuclear Accumulation of RASSF6 Tumor Suppressor Protein via CDK9 and BAF53 To Regulate p53 Target Gene Transcription. (PMID:34898277)
• Kindlin-3 and RASSF6 are probable biomarkers for predicting metastasis in cutaneous melanoma. (PMID:35048636)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rassf6	ENSDARG00000000804
mus_musculus	Rassf6	ENSMUSG00000029370
rattus_norvegicus	Rassf6	ENSRNOG00000002866
drosophila_melanogaster	Rassf	FBGN0039055
caenorhabditis_elegans		WBGENE00011995

Paralogs (5): RASSF1 (ENSG00000068028), RASSF2 (ENSG00000101265), RASSF4 (ENSG00000107551), RASSF3 (ENSG00000153179), RASSF5 (ENSG00000266094)

Protein

Protein identifiers

Ras association domain-containing protein 6 — Q6ZTQ3 (reviewed: Q6ZTQ3)

All UniProt accessions (1): Q6ZTQ3

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the induction of apoptosis, through both caspase-dependent and caspase-independent pathways. May act as a Ras effector protein. May suppress the serum-induced basal levels of NF-kappa-B.

Subunit / interactions. Interacts with MOAP1. Interaction with activated KRAS is still a matter of debate: interaction has been shown in the mouse, but not in human. Lack of interaction with MRAS, NRAS nor RRAS2 has also been reported.

Tissue specificity. Highest expression in thymus, kidney and placenta. Also detected in colon, small intestine and lung. Tends to be down-regulated in 30-60% of tumors derived from breast, colon, kidney liver, rectum, pancreas, stomach and the thyroid gland compared to the normal counterpart.

Isoforms (4)

UniProt ID	Names	Canonical?
Q6ZTQ3-1	1	yes
Q6ZTQ3-2	2, A
Q6ZTQ3-3	3, B
Q6ZTQ3-4	4

RefSeq proteins (4): NP_001257320, NP_001257321, NP_803876, NP_958834 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000159	RA_dom	Domain
IPR011524	SARAH_dom	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR033614	RASSF1-6	Family
IPR049787	SARAH_RASSF6	Domain

Pfam: PF00788, PF16517

UniProt features (9 total): splice variant 3, domain 2, sequence variant 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZTQ3-F1	70.38	0.38

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 (1): 187

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 108 (showing top): FOXO4_01, chr4q13, FREAC3_01, TCCCRNNRTGC_UNKNOWN, BOCHKIS_FOXA2_TARGETS, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_WITH_LMP1_UP, MIKKELSEN_ES_ICP_WITH_H3K4ME3, BAKKER_FOXO3_TARGETS_DN, WAKABAYASHI_ADIPOGENESIS_PPARG_RXRA_BOUND_8D, WAMUNYOKOLI_OVARIAN_CANCER_GRADES_1_2_UP, CREB3L4_TARGET_GENES, DACH1_TARGET_GENES, ELF2_TARGET_GENES, FEV_TARGET_GENES, HOXB4_TARGET_GENES

GO Biological Process (4): apoptotic process (GO:0006915), signal transduction (GO:0007165), positive regulation of apoptotic process (GO:0043065), regulation of apoptotic process (GO:0042981)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
apoptotic process	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
regulation of programmed cell death	1
binding	1

Protein interactions and networks

STRING

660 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RASSF6	MOAP1	Q96BY2	866
RASSF6	RASSF7	Q02833	842
RASSF6	RASSF10	A6NK89	778
RASSF6	ENDOG	Q14249	698
RASSF6	RASSF3	Q86WH2	647
RASSF6	RASSF8	Q8NHQ8	609
RASSF6	THBS4	P35443	512
RASSF6	RASSF9	O75901	507
RASSF6	AIFM1	O95831	494
RASSF6	HRAS	P01112	462
RASSF6	SAV1	Q9H4B6	448
RASSF6	RASSF1	Q9NS23	439
RASSF6	AMER2	Q8N7J2	429
RASSF6	ARHGEF4	Q9NR80	424
RASSF6	CXCR2	P25025	423

IntAct

259 interactions, top by confidence:

A	B	Type	Score
RASSF6	STK4	psi-mi:“MI:0915”(physical association)	0.780
STK4	RASSF6	psi-mi:“MI:0915”(physical association)	0.780
RASSF6	STK4	psi-mi:“MI:0914”(association)	0.780
RASSF6	STK3	psi-mi:“MI:0915”(physical association)	0.660
RASSF6	DLG1	psi-mi:“MI:0915”(physical association)	0.610
STK4	STRN	psi-mi:“MI:0914”(association)	0.610
RASSF6	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.610
RASSF6	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.610
RASSF6	DLG4	psi-mi:“MI:0407”(direct interaction)	0.610
RASSF6	SNX27	psi-mi:“MI:0407”(direct interaction)	0.610
RASSF6	MAST2	psi-mi:“MI:0407”(direct interaction)	0.610
MAGI2	RASSF6	psi-mi:“MI:0407”(direct interaction)	0.610
RASSF6	DLG1	psi-mi:“MI:0407”(direct interaction)	0.610
PDZRN4	RASSF6	psi-mi:“MI:0407”(direct interaction)	0.610
PDZRN4	RASSF6	psi-mi:“MI:0915”(physical association)	0.610
RASSF6	SCRIB	psi-mi:“MI:0915”(physical association)	0.610
DLG4	RASSF6	psi-mi:“MI:0915”(physical association)	0.610
SNX27	RASSF6	psi-mi:“MI:0407”(direct interaction)	0.610
MAST2	RASSF6	psi-mi:“MI:0915”(physical association)	0.610

BioGRID (31): KDM3A (Affinity Capture-MS), STK3 (Affinity Capture-MS), STK4 (Affinity Capture-MS), HECTD1 (Affinity Capture-MS), RASSF6 (Affinity Capture-MS), AMY1A (Affinity Capture-MS), STK4 (Affinity Capture-MS), STK3 (Affinity Capture-MS), KDM3A (Affinity Capture-MS), STK4 (Affinity Capture-MS), STK3 (Affinity Capture-MS), RASSF6 (Affinity Capture-Western), UNC119 (Affinity Capture-Western), UNC119 (Co-purification), RASSF6 (Reconstituted Complex)

ESM2 similar proteins: A2AD83, A2CEA7, A5DHC9, A6H8H2, A7TKX9, A8WG21, B7ZC32, F1Q506, F1REV3, F8WLE0, O14827, P10686, P32019, P70392, P97369, P97433, Q05AK5, Q08826, Q09178, Q0IIL5, Q17QS1, Q28HD5, Q3U1T9, Q4FZZ1, Q4QR82, Q5U2S5, Q5VZ89, Q62077, Q6BIS2, Q6CY25, Q6DDY6, Q6FR40, Q6P3S1, Q6P5D3, Q6P8Y7, Q6ZTQ3, Q75R65, Q7Z7A4, Q80UQ2, Q8BX57

Diamond homologs: O35141, Q22744, Q5EBH1, Q6ZTQ3, Q86WH2, Q8WWW0, Q99MK9, Q99P51, Q9NS23, Q9R1K8, Q9Z1S3, P50749, Q3B7D5, Q4QR82, Q566C5, Q80UQ2, Q8BMS9, Q8CB96, Q9H2L5, A4IJ06, A8KBH6, A8XQD5, D3ZEY4, O45818, O94806, O95267, P04409, P05126, P05128, P05129, P05696, P05771, P05772, P09215, P09216, P10102, P10829, P10830, P13677, P13678

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RASSF6	down-regulates	STK3	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 104 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
Ras activation upon Ca2+ influx through NMDA receptor	5	42.6×	4e-06
Signaling by Hippo	5	40.6×	4e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	40.6×	4e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	40.6×	4e-06
Long-term potentiation	5	35.5×	7e-06
Tight junction interactions	6	33.0×	2e-06
Assembly and cell surface presentation of NMDA receptors	8	30.3×	2e-08
Neurexins and neuroligins	9	26.4×	1e-08

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	14	83.9×	7e-22
protein localization to synapse	7	55.3×	6e-09
receptor clustering	8	51.5×	6e-10
regulation of postsynaptic membrane neurotransmitter receptor levels	6	30.7×	3e-06
establishment or maintenance of cell polarity	6	24.8×	7e-06
bicellular tight junction assembly	6	20.4×	2e-05
protein-containing complex assembly	10	11.7×	1e-06
negative regulation of ERK1 and ERK2 cascade	5	11.1×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1764 predictions. Top by Δscore:

Variant	Effect	Δscore
4:73576611:A:AC	donor_gain	1.0000
4:73576612:C:CC	donor_gain	1.0000
4:73576612:CAT:C	donor_gain	1.0000
4:73576612:CATCA:C	donor_gain	1.0000
4:73576614:T:TA	donor_gain	1.0000
4:73576616:A:AC	donor_gain	1.0000
4:73576617:C:CC	donor_gain	1.0000
4:73585178:A:AC	donor_gain	1.0000
4:73585179:C:CC	donor_gain	1.0000
4:73593449:AC:A	donor_gain	1.0000
4:73593450:CC:C	donor_gain	1.0000
4:73593594:C:CC	acceptor_gain	1.0000
4:73576408:A:AC	donor_gain	0.9900
4:73576409:C:CC	donor_gain	0.9900
4:73576617:CTG:C	donor_gain	0.9900
4:73576629:T:TA	donor_gain	0.9900
4:73576732:C:CC	acceptor_gain	0.9900
4:73581815:ACCT:A	donor_gain	0.9900
4:73581816:CCTC:C	donor_gain	0.9900
4:73585175:CTTA:C	donor_gain	0.9900
4:73585178:ACTT:A	donor_gain	0.9900
4:73585179:CTT:C	donor_gain	0.9900
4:73585179:CTTC:C	donor_gain	0.9900
4:73587935:C:CC	acceptor_gain	0.9900
4:73593444:AGCTT:A	donor_loss	0.9900
4:73593445:GCTT:G	donor_loss	0.9900
4:73593446:CTT:C	donor_loss	0.9900
4:73593447:TTA:T	donor_loss	0.9900
4:73593448:T:TG	donor_loss	0.9900
4:73593449:A:AC	donor_gain	0.9900

AlphaMissense

2270 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:73582192:A:C	F254L	0.990
4:73582192:A:T	F254L	0.990
4:73582194:A:G	F254L	0.990
4:73581845:A:C	F263L	0.987
4:73581845:A:T	F263L	0.987
4:73581847:A:G	F263L	0.987
4:73593548:A:G	W96R	0.982
4:73593548:A:T	W96R	0.982
4:73576701:G:T	P283Q	0.976
4:73581846:A:G	F263S	0.974
4:73582279:G:C	F225L	0.974
4:73582279:G:T	F225L	0.974
4:73582281:A:G	F225L	0.974
4:73581840:A:T	L265H	0.971
4:73593546:C:A	W96C	0.970
4:73593546:C:G	W96C	0.970
4:73576701:G:C	P283R	0.967
4:73582237:A:C	S239R	0.965
4:73582237:A:T	S239R	0.965
4:73582239:T:G	S239R	0.965
4:73576688:C:A	R287S	0.964
4:73576688:C:G	R287S	0.964
4:73593566:C:G	G90R	0.962
4:73593566:C:T	G90R	0.962
4:73576647:A:T	L301H	0.961
4:73581840:A:C	L265R	0.959
4:73582202:A:G	L251P	0.958
4:73576686:A:G	L288P	0.957
4:73582205:A:G	L250P	0.957
4:73576647:A:G	L301P	0.955

dbSNP variants (sampled 300 via entrez): RS1000067685 (4:73599823 C>T), RS1000077508 (4:73599504 C>T), RS1000279750 (4:73597888 T>C), RS1000285088 (4:73611318 C>A), RS1000312996 (4:73598187 T>C), RS10003721 (4:73575067 T>C), RS1000372567 (4:73593527 GTA>G), RS1000404652 (4:73587396 A>G), RS10004505 (4:73572281 G>A), RS1000545887 (4:73577164 C>G,T), RS1000563346 (4:73575891 T>C), RS1000572867 (4:73617867 C>T), RS1000611480 (4:73604510 A>C), RS1000724755 (4:73588631 C>A,T), RS1000729418 (4:73582554 A>C)

Disease associations

OMIM: gene MIM:612620 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST001942_8	Prostate cancer	5.000000e-13
GCST005447_42	Total cholesterol levels in LDL	8.000000e-12
GCST005448_14	Serum total cholesterol levels	2.000000e-14
GCST005481_7	Large LDL particle concentration	1.000000e-08
GCST005483_8	Total cholesterol levels in large LDL	3.000000e-08
GCST005484_6	Cholesterol ester levels in large LDL	3.000000e-08
GCST005485_1	Free cholesterol levels in large LDL	4.000000e-08
GCST005486_8	Medium LDL particle concentration	3.000000e-09
GCST005488_8	Total cholesterol levels in medium LDL	9.000000e-09
GCST005489_9	Cholesterol ester levels in medium LDL	5.000000e-09
GCST005490_12	Small LDL particle concentration	3.000000e-20
GCST005491_22	Total cholesterol levels in small LDL	6.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0008589	esterified cholesterol measurement
EFO:0008591	free cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases methylation	6
mercuric bromide	increases expression, affects cotreatment	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	decreases expression, increases expression	2
methyleugenol	increases expression	1
bisphenol A	increases expression	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
tamibarotene	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
NSC 689534	affects binding, increases expression	1
Panobinostat	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Copper	affects binding, increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Lipopolysaccharides	increases expression, decreases reaction	1
Tetrachlorodibenzodioxin	affects expression	1
Tobacco Smoke Pollution	decreases expression	1
8-Bromo Cyclic Adenosine Monophosphate	increases 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_5114	ACC-MESO-4	Cancer cell line	Male

Clinical trials (associated diseases)

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