RFX1

Summary

RFX1 (regulatory factor X1, HGNC:9982) is a protein-coding gene on chromosome 19p13.12, encoding MHC class II regulatory factor RFX1 (P22670). Regulatory factor essential for MHC class II genes expression.

This gene encodes a member of the regulatory factor X (RFX) family of transcription factors, which are characterized by a winged-helix DNA-binding domain. The encoded transcription factor contains an N-terminal activation domain and a C-terminal repression domain, and may activate or repress target gene expression depending on cellular context. This transcription factor has been shown to regulate a wide variety of genes involved in immunity and cancer, including the MHC class II genes and genes that may be involved in cancer progression. This gene exhibits altered expression in glioblastoma and the autoimmune disease systemic lupus erythematosis (SLE).

Source: NCBI Gene 5989 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 168 total
• Transcription factor: yes — 28 downstream targets (CollecTRI)
• MANE Select transcript: NM_002918

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9982
Approved symbol	RFX1
Name	regulatory factor X1
Location	19p13.12
Locus type	gene with protein product
Status	Approved
Aliases	EF-C
Ensembl gene	ENSG00000132005
Ensembl biotype	protein_coding
OMIM	600006
Entrez	5989

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 10 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000254325, ENST00000586913, ENST00000588520, ENST00000588885, ENST00000589239, ENST00000589760, ENST00000589937, ENST00000872111, ENST00000872112, ENST00000872113, ENST00000872114, ENST00000872115, ENST00000872116, ENST00000872117, ENST00000872118

RefSeq mRNA: 1 — MANE Select: NM_002918 NM_002918

CCDS: CCDS12301

Canonical transcript exons

ENST00000254325 — 21 exons

Exon	Start	End
ENSE00000902136	13962994	13963039
ENSE00000902138	13963538	13963746
ENSE00000902139	13963858	13964007
ENSE00000902140	13965449	13965546
ENSE00000902141	13965626	13965777
ENSE00000902142	13966421	13966530
ENSE00000902143	13966633	13966751
ENSE00000902144	13968565	13968680
ENSE00000902145	13968775	13968894
ENSE00000902146	13969994	13970175
ENSE00001385967	13961530	13962864
ENSE00001794399	13963122	13963275
ENSE00002878713	14006103	14006320
ENSE00003533228	13980573	13980689
ENSE00003544596	13983486	13983595
ENSE00003553019	13993525	13993895
ENSE00003589069	13983187	13983270
ENSE00003630933	13972743	13973127
ENSE00003647392	13982121	13982228
ENSE00003647433	13979447	13979542
ENSE00003693090	13977992	13978086

Expression profiles

Bgee: expression breadth ubiquitous, 137 present calls, max score 87.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.7732 / max 132.3765, expressed in 1762 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179587	9.3497	1758
179588	0.3220	129
179582	0.0675	38
179589	0.0340	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	87.01	gold quality
left testis	UBERON:0004533	86.85	gold quality
testis	UBERON:0000473	85.72	gold quality
granulocyte	CL:0000094	85.42	gold quality
pituitary gland	UBERON:0000007	85.11	gold quality
right uterine tube	UBERON:0001302	84.16	gold quality
adenohypophysis	UBERON:0002196	84.05	gold quality
blood	UBERON:0000178	83.78	gold quality
lower esophagus mucosa	UBERON:0035834	82.50	gold quality
right hemisphere of cerebellum	UBERON:0014890	82.41	gold quality
apex of heart	UBERON:0002098	82.10	gold quality
cerebellum	UBERON:0002037	81.73	gold quality
cerebellar hemisphere	UBERON:0002245	81.68	gold quality
cerebellar cortex	UBERON:0002129	81.62	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.63	gold quality
right lobe of thyroid gland	UBERON:0001119	80.42	gold quality
bone marrow cell	CL:0002092	80.39	gold quality
endocervix	UBERON:0000458	80.19	gold quality
left lobe of thyroid gland	UBERON:0001120	79.72	gold quality
leukocyte	CL:0000738	79.43	gold quality
gastrocnemius	UBERON:0001388	79.36	gold quality
mucosa of transverse colon	UBERON:0004991	79.30	gold quality
thyroid gland	UBERON:0002046	79.26	gold quality
monocyte	CL:0000576	79.07	gold quality
heart left ventricle	UBERON:0002084	78.92	gold quality
ectocervix	UBERON:0012249	78.90	gold quality
hindlimb stylopod muscle	UBERON:0004252	78.73	gold quality
left ovary	UBERON:0002119	78.46	gold quality
spleen	UBERON:0002106	78.36	gold quality
right ovary	UBERON:0002118	78.35	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.30

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

28 targets.

Target	Regulation
ADAM2
ADGRG1
CD70	Unknown
CD74
CIITA	Unknown
COL1A2	Activation
CSH1	Repression
FGF1	Unknown
H1-6
HDAC1	Unknown
HLA-DMB	Unknown
HLA-DOB	Unknown
HLA-DPB1	Unknown
HLA-DRA	Unknown
HLA-E	Unknown
ID2	Unknown
IL5RA	Unknown
ITGAL	Unknown
MAP1A	Repression
MSLN	Unknown
MYC	Repression
PCNA	Repression
PTPN6
RPL30	Unknown
SLC1A1	Activation
SPATA4	Unknown
SUPT7L
TGFB2	Unknown

miRNA regulators (miRDB)

76 targeting RFX1, 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-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-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718

Literature-anchored findings (GeneRIF, showing 33)

• Data show that two regulatory factor for X box (RFX1 and 3) binding sites in exon1 of both the mouse and human microtubule-associated protein (MAP1A) gene are important for effective transcriptional repression in non-neuronal cells. (PMID:12411430)
• Disruption of the RFX site within 263P blunts repressor activity in transfected GC cells; however, repression is only abolished when both PSE-A/RFX and PSE-B/NF-1 sites are mutated. (PMID:12624117)
• novel role for the RFX family of transcription factors as modulators of Ras signalling in epithelial cells (PMID:15024578)
• RFX1 gene may be epigenetically silenced in human gliomas and involved in glioma tumorigenesis. (PMID:15334059)
• Six novel S’-Y’ regulatory modules have been identified that are controlled by the human major histocompatibility class II-specific regulatory factor RFX complex. (PMID:15528357)
• evidence for a common mechanism for Crt1 and Rfx1 expression and for the conservation of their mode of action in response to a DNA replication block in yeasts and humans (PMID:16287876)
• The binding of alpha Adducin to RFX-I and their nuclear co-localization suggests that Adducin can have a role in modulating the transcriptional regulating activity of RFX-I. (PMID:16289097)
• results demonstrate that RFX1 and RFX5 differentially interact with class I HDACs underlying the different pathways when repressing collagen synthesis (PMID:16464847)
• RFX1 mediates the immediate early response of the Id2 gene by serum stimulation and suggest that the function of RFX1 is regulated intramolecularly in its suppression in growth-arrested cells. (PMID:17630394)
• RFX1 specifically bind to promoter region and negatively regulate the transcription of the human PNRC gene. (PMID:19334528)
• RFX and/or enhanceosome assembly plays a key role independent of transcriptional coactivator CIITA in protecting major histocompatibility class II antigen promoters against DNA methylation. (PMID:19620312)
• RFX1 may negatively regulate the self-renewal of GBM-SCs through modulating FGF-1B and FGF1 expression levels by binding the 18-bp cis-elements of the F1B promoter. (PMID:20189986)
• regulates autoimmunity via epigenetic modifications in T cells of systemic lupus erythematosus patients (PMID:20223637)
• We show binding of RFX proteins to an evolutionarily conserved X-box in the ALMS1 proximal promoter and present evidence that these proteins are responsible for ALMS1 transc (PMID:20381594)
• RFX1 recruits SUV39H1 to the promoter regions of the CD11a and CD70 genes in CD4(+) T cells, thereby regulating local H3K9 tri-methylation levels. (PMID:21192791)
• in serum- or IGF-1-stimulated breast cancer MCF-7 cells, JNK induces SHP1 expression through the binding of AP-4 and RFX-1 transcription factors to the epithelial tissue-specific SHP1 promoter. (PMID:21719561)
• Taken together, this study suggests ciliogenic RFX transcription factors regulate FGF-1B promoter activity and the maintenance of F1BGFP(+) NSPCs and GBM-SCs. (PMID:22415835)
• NLRC5-mediated histocompatibiility class I gene induction requires the W/S and X1, X2 cis-regulatory elements. (PMID:22490869)
• RFX1 reduces cell proliferation through inhibiting the TGFbeta2-ERK signaling pathway. RFX1 blocks TGFbeta2 expression through its direct action on TGFbeta2 transcription. (PMID:22582395)
• regulatory factor 1 directly regulates CD44 expression in glioblastoma (PMID:24526308)
• Data indicate that regulatory factor X transcription factor RFX-1 regulates SC-2001-mediated SHP-1 Phosphatase transcription in hepatocellular carcinoma cells. (PMID:24952874)
• therapeutic targets for childhood severe asthmatics identified thru DNA microarray (PMID:25979195)
• Data show that transcription factor regulatory factor X 1 (RFX1) protein expression can be tightly regulated by polyubiquitination-mediated proteosomal degradation via STIP1 homology and U-box containing protein 1 (STUB1). (PMID:27283392)
• induction of ciliogenesis increases the expression of RFX and dyslexia candidate genes (PMID:27451412)
• Results show that reduced miRNA-124 improved microglia activation and up-regulated its downstream target RFX1, indicating that RFX1, as one of the target transcripts, facilitates microglial activation by miR-124 regulation; identified the binding site through which RFX1 directly regulates ApoE, may explain the missing link between decreased miRNA-124 and ineffective Abeta uptaking during aging. (PMID:28003160)
• RFX1 interacts with the D sequence of adeno-associated virus inverted terminal repeat and regulates AAV transduction. (PMID:29317724)
• Findings indicate that RFX1 functions downstream of STAT3 and phosphorylated STAT3 can inhibit RFX1 expression and suggest a unique role for RFX1 in Th17-related autoimmune diseases. (PMID:29422534)
• RFX1 expression was significantly lower in HCC tissues compared to the corresponding non-tumor tissues. In vitro studies suggested that knocking down RFX1 facilitated HCC cell invasion, while overexpression of RFX1 reduced the invasion of HCC cells. RFX1 regulated expression of some epithelial-mesenchymal transition markers. (PMID:29764705)
• the recruitment of PP1c to promoters may be a mechanism by which RFX1 regulates the target genes. (PMID:30654936)
• Results show that RFX1 expression deficiency leads to the overexpression of TLR4 and the activation of CD14(+) monocytes in coronary artery disease (CAD) patients by regulating DNA methylation and histone modifications, which highlights the vital role of RFX1 in the pathogenesis of CAD. (PMID:30857550)
• RFX1-mediated CCN3 induction that may support chondrocyte survival under starved conditions. (PMID:33655492)
• RFX transcription factors control a miR-150/PDAP1 axis that restrains the proliferation of human T cells. (PMID:35143476)
• RXR agonist, Bexarotene, effectively reduces drug resistance via regulation of RFX1 in embryonic carcinoma cells. (PMID:37301270)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rfx1a	ENSDARG00000005883
danio_rerio	rfx1b	ENSDARG00000075904
mus_musculus	Rfx1	ENSMUSG00000031706
rattus_norvegicus	Rfx1	ENSRNOG00000006049
drosophila_melanogaster	Rfx	FBGN0020379

Paralogs (7): RFX3 (ENSG00000080298), RFX2 (ENSG00000087903), RFX4 (ENSG00000111783), RFX5 (ENSG00000143390), RFX7 (ENSG00000181827), RFX6 (ENSG00000185002), RFX8 (ENSG00000196460)

Protein

Protein identifiers

MHC class II regulatory factor RFX1 — P22670 (reviewed: P22670)

Alternative names: Enhancer factor C, Regulatory factor X 1, Transcription factor RFX1

All UniProt accessions (2): P22670, K7EIZ8

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory factor essential for MHC class II genes expression. Binds to the X boxes of MHC class II genes. Also binds to an inverted repeat (ENH1) required for hepatitis B virus genes expression and to the most upstream element (alpha) of the RPL30 promoter.

Subunit / interactions. Homodimer; binds DNA as a homodimer. Heterodimer; heterodimerizes with RFX2 and RFX3.

Subcellular location. Nucleus.

Similarity. Belongs to the RFX family.

RefSeq proteins (1): NP_002909* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003150	DNA-bd_RFX	Domain
IPR007668	RFX1_trans_act	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR039779	RFX-like	Family
IPR057321	RFX1-4/6/8-like_BCD	Domain

Pfam: PF02257, PF04589, PF25340

UniProt features (27 total): compositionally biased region 10, region of interest 5, modified residue 3, helix 3, strand 3, chain 1, DNA-binding region 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1DP7	X-RAY DIFFRACTION	1.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22670-F1	60.65	0.37

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 (3): 60, 978, 979

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 179 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GCANCTGNY_MYOD_Q6, TTTGTAG_MIR520D, TGACCTY_ERR1_Q2, GGGTGGRR_PAX4_03, GTGCCTT_MIR506, BROWNE_HCMV_INFECTION_48HR_DN, E4F1_Q6, ATF3_Q6, MORF_EPHA7, MORF_RAB3A, MORF_WNT1, TGCCTTA_MIR124A, MORF_IL9, AP2_Q6_01

GO Biological Process (3): regulation of transcription by RNA polymerase II (GO:0006357), immune response (GO:0006955), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (6): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515)

GO Cellular Component (3): chromatin (GO:0000785), nucleoplasm (GO:0005654), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
cellular anatomical structure	2
transcription by RNA polymerase II	1
immune system process	1
response to stimulus	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
binding	1
chromosome	1
nuclear lumen	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1662 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RFX1	CREB1	P16220	986
RFX1	RFXAP	O00287	961
RFX1	CIITA	P33076	958
RFX1	RFXANK	O14593	954
RFX1	HDAC1	Q13547	842
RFX1	SUV39H1	O43463	832
RFX1	RPL30	P04645	794
RFX1	DNMT1	P26358	744
RFX1	IFT88	Q13099	741
RFX1	NFYA	P23511	651
RFX1	HLA-DRA	P01903	647
RFX1	NFYC	Q13952	636
RFX1	NLRC5	Q86WI3	606
RFX1	FOXJ1	Q92949	603
RFX1	RFX5	P48382	585

IntAct

72 interactions, top by confidence:

A	B	Type	Score
FOXJ1	RFX1	psi-mi:“MI:0914”(association)	0.730
RFX3	RFX1	psi-mi:“MI:0914”(association)	0.730
FOXN2	RFX1	psi-mi:“MI:0915”(physical association)	0.710
FOXN2	RFX1	psi-mi:“MI:0914”(association)	0.710
ADD1	RFX1	psi-mi:“MI:0915”(physical association)	0.540
RFX1	ADD1	psi-mi:“MI:0403”(colocalization)	0.540
FBXL3	RFX1	psi-mi:“MI:0914”(association)	0.530
HSPB8	VWA8	psi-mi:“MI:0914”(association)	0.530
FHL2	CNOT1	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
FOXJ1	PEX14	psi-mi:“MI:0914”(association)	0.530
FOXN3	RFX1	psi-mi:“MI:0914”(association)	0.530
RRP8	MAGEB2	psi-mi:“MI:0914”(association)	0.530
HDAC1	RFX1	psi-mi:“MI:0915”(physical association)	0.530
RFX1	SMAD4	psi-mi:“MI:0915”(physical association)	0.370
SMAD1	RFX1	psi-mi:“MI:0915”(physical association)	0.370
RFX1	SMAD9	psi-mi:“MI:0915”(physical association)	0.370
FOXJ2	TCERG1	psi-mi:“MI:0914”(association)	0.350
FOXJ1	ACSL4	psi-mi:“MI:0914”(association)	0.350

BioGRID (97): RFX1 (Affinity Capture-MS), RFX1 (Affinity Capture-MS), RFX1 (Affinity Capture-MS), RFX1 (Affinity Capture-MS), RFX1 (Affinity Capture-Western), STUB1 (Affinity Capture-Western), HSPA8 (Affinity Capture-Western), RFX1 (Affinity Capture-MS), RFX1 (Affinity Capture-MS), RFX1 (Affinity Capture-MS), RFX1 (Affinity Capture-MS), RFX1 (Affinity Capture-MS), RFX1 (Affinity Capture-MS), RFX1 (Affinity Capture-MS), RFX1 (Affinity Capture-MS)

ESM2 similar proteins: A0JMF8, A2RSY1, A6QLW9, B1WAV2, B2GV50, O60271, O75069, O77627, P05412, P05627, P0C090, P17325, P22670, P48377, P48378, P48379, P48380, P48381, P56432, Q0V989, Q0V9K5, Q16656, Q32NR3, Q3KR73, Q499B3, Q49GP3, Q4R3I8, Q4R3Z4, Q4V872, Q4VGL6, Q58A65, Q5EAP5, Q5EY87, Q5RDR2, Q5RJA1, Q5TC82, Q62739, Q66IV1, Q6NRE7, Q6NUC6

Diamond homologs: A0A1L8GWK2, A0A1L8H0H2, A0JMF8, A2BGA0, A6QLW9, B1WAV2, B2GV50, D2HNW6, F8VPJ6, P22670, P48377, P48378, P48379, P48380, P48381, P48382, P48743, Q09555, Q0V9K5, Q2KHR2, Q32NR3, Q33E94, Q4R3I8, Q4R3Z4, Q59V88, Q5EAP5, Q5RDR2, Q5RJA1, Q7TNK1, Q8C7R7, Q8HWS3, Q9JL61, D3YU81, P48383, Q6ZV50, Q5AMQ6

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
RFX1	“down-regulates quantity by repression”	MYC	“transcriptional regulation”
RFX1	“up-regulates quantity by expression”	HLA-DOB	“transcriptional regulation”
RFX1	up-regulates	ABL1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 72 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.

GO biological processes:

GO term	Partners	Fold	FDR
osteoblast differentiation	6	11.0×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	127
Likely benign	6
Benign	13

Top pathogenic / likely-pathogenic (0)

SpliceAI

3476 predictions. Top by Δscore:

Variant	Effect	Δscore
19:13962860:CTCGT:C	acceptor_gain	1.0000
19:13962862:CGT:C	acceptor_gain	1.0000
19:13962865:C:CC	acceptor_gain	1.0000
19:13962989:CCTA:C	donor_loss	1.0000
19:13962990:CTA:C	donor_loss	1.0000
19:13962991:TA:T	donor_loss	1.0000
19:13962992:ACCT:A	donor_loss	1.0000
19:13962993:C:CT	donor_loss	1.0000
19:13963035:GCGAA:G	acceptor_gain	1.0000
19:13963036:CGAA:C	acceptor_gain	1.0000
19:13963036:CGAAC:C	acceptor_gain	1.0000
19:13963037:GAA:G	acceptor_gain	1.0000
19:13963038:AA:A	acceptor_gain	1.0000
19:13963039:AC:A	acceptor_loss	1.0000
19:13963040:C:CC	acceptor_gain	1.0000
19:13963040:CTGGA:C	acceptor_loss	1.0000
19:13963117:CGCA:C	donor_loss	1.0000
19:13963119:CACCT:C	donor_loss	1.0000
19:13963121:C:CT	donor_loss	1.0000
19:13963121:CCTCG:C	donor_gain	1.0000
19:13963150:C:CA	donor_gain	1.0000
19:13963271:TGGAG:T	acceptor_gain	1.0000
19:13963272:GGAG:G	acceptor_gain	1.0000
19:13963273:GAG:G	acceptor_gain	1.0000
19:13963274:AG:A	acceptor_gain	1.0000
19:13963276:C:CC	acceptor_gain	1.0000
19:13963282:A:AC	acceptor_gain	1.0000
19:13963282:A:C	acceptor_gain	1.0000
19:13963289:C:CT	acceptor_gain	1.0000
19:13963533:CGCA:C	donor_loss	1.0000

AlphaMissense

6313 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:13963132:A:T	V905D	1.000
19:13963162:G:T	A895D	1.000
19:13963163:C:G	A895P	1.000
19:13963168:C:G	R893P	1.000
19:13963173:C:A	E891D	1.000
19:13963173:C:G	E891D	1.000
19:13963174:T:A	E891V	1.000
19:13963175:C:T	E891K	1.000
19:13963180:A:G	L889P	1.000
19:13963184:A:C	Y888D	1.000
19:13963189:A:T	M886K	1.000
19:13963193:A:C	Y885D	1.000
19:13963194:C:A	E884D	1.000
19:13963194:C:G	E884D	1.000
19:13963195:T:A	E884V	1.000
19:13963195:T:C	E884G	1.000
19:13963195:T:G	E884A	1.000
19:13963196:C:G	E884Q	1.000
19:13963196:C:T	E884K	1.000
19:13963197:G:C	D883E	1.000
19:13963197:G:T	D883E	1.000
19:13963198:T:A	D883V	1.000
19:13963198:T:C	D883G	1.000
19:13963198:T:G	D883A	1.000
19:13963199:C:A	D883Y	1.000
19:13963199:C:G	D883H	1.000
19:13963199:C:T	D883N	1.000
19:13963202:A:C	Y882D	1.000
19:13963204:A:C	L881R	1.000
19:13963204:A:G	L881P	1.000

dbSNP variants (sampled 300 via entrez): RS1000005785 (19:13983709 C>A,T), RS1000032415 (19:14003290 GC>G), RS1000174432 (19:13988592 T>A,C), RS1000199008 (19:13992823 CAA>C), RS1000232840 (19:13994545 G>A,T), RS1000236880 (19:13978460 G>C), RS1000286740 (19:13998638 A>G), RS1000346766 (19:13994347 A>C,G), RS1000350953 (19:13962528 CTGAT>C), RS1000423736 (19:13998976 T>A), RS1000607191 (19:14004674 C>A,T), RS1000617445 (19:13967696 C>A,G,T), RS1000698153 (19:13993184 A>G,T), RS1000710291 (19:14005490 G>A,T), RS1000765144 (19:13973554 G>A)

Disease associations

OMIM: gene MIM:600006 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation, affects cotreatment	2
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
beta-methylcholine	affects expression	1
abrine	increases expression	1
Vorinostat	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Testosterone	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1

Clinical trials (associated diseases)

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