POLR2D

Summary

POLR2D (RNA polymerase II subunit D, HGNC:9191) is a protein-coding gene on chromosome 2q14.3, encoding DNA-directed RNA polymerase II subunit RPB4 (O15514). Core component of RNA polymerase II (Pol II), a DNA-dependent RNA polymerase which synthesizes mRNA precursors and many functional non-coding RNAs using the four ribonucleoside triphosphates as substrates. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

This gene encodes the fourth largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. In yeast, this polymerase subunit is associated with the polymerase under suboptimal growth conditions and may have a stress protective role. A sequence for a ribosomal pseudogene is contained within the 3’ untranslated region of the transcript from this gene.

Source: NCBI Gene 5433 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 9 total
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_004805

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9191
Approved symbol	POLR2D
Name	RNA polymerase II subunit D
Location	2q14.3
Locus type	gene with protein product
Status	Approved
Aliases	RPB4
Ensembl gene	ENSG00000144231
Ensembl biotype	protein_coding
OMIM	606017
Entrez	5433

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000272645, ENST00000409698, ENST00000409955, ENST00000487079, ENST00000891594

RefSeq mRNA: 1 — MANE Select: NM_004805 NM_004805

CCDS: CCDS2151

Canonical transcript exons

ENST00000272645 — 4 exons

Exon	Start	End
ENSE00001137843	127850590	127850685
ENSE00001337644	127843553	127848185
ENSE00001907079	127858028	127858155
ENSE00003605601	127852925	127853105

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 95.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.1542 / max 170.9612, expressed in 1808 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
30582	24.4844	1808
30577	0.6160	381
30580	0.0428	3
30579	0.0080	3
30581	0.0030	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	95.41	gold quality
left testis	UBERON:0004533	94.66	gold quality
right testis	UBERON:0004534	94.08	gold quality
oviduct epithelium	UBERON:0004804	93.32	gold quality
testis	UBERON:0000473	93.20	gold quality
pancreatic ductal cell	CL:0002079	92.58	gold quality
tibialis anterior	UBERON:0001385	90.66	gold quality
embryo	UBERON:0000922	90.63	gold quality
ganglionic eminence	UBERON:0004023	90.63	gold quality
ventricular zone	UBERON:0003053	90.45	gold quality
adrenal tissue	UBERON:0018303	89.98	gold quality
islet of Langerhans	UBERON:0000006	89.96	gold quality
gastrocnemius	UBERON:0001388	89.46	gold quality
muscle of leg	UBERON:0001383	89.40	gold quality
skeletal muscle organ	UBERON:0014892	89.06	gold quality
quadriceps femoris	UBERON:0001377	89.00	silver quality
vastus lateralis	UBERON:0001379	88.88	gold quality
medial globus pallidus	UBERON:0002477	88.74	silver quality
hindlimb stylopod muscle	UBERON:0004252	88.47	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.94	gold quality
skeletal muscle tissue	UBERON:0001134	87.57	gold quality
left ventricle myocardium	UBERON:0006566	87.53	silver quality
stromal cell of endometrium	CL:0002255	87.49	gold quality
globus pallidus	UBERON:0001875	87.33	silver quality
muscle tissue	UBERON:0002385	86.98	gold quality
bone marrow cell	CL:0002092	86.89	gold quality
adult organism	UBERON:0007023	86.77	gold quality
smooth muscle tissue	UBERON:0001135	86.36	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	86.08	gold quality
pigmented layer of retina	UBERON:0001782	86.01	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.39

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

101 targeting POLR2D, 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-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3658	99.96	73.87	4379
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6875-3P	99.82	70.26	2983

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 1)

• Identification of the RNA binding region of Rpb4. (PMID:16282592)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	polr2d	ENSDARG00000076509
mus_musculus	Polr2d	ENSMUSG00000024258
rattus_norvegicus	Polr2d	ENSRNOG00000016231
drosophila_melanogaster	Polr2D	FBGN0263757
caenorhabditis_elegans		WBGENE00018391

Protein

Protein identifiers

DNA-directed RNA polymerase II subunit RPB4 — O15514 (reviewed: O15514)

Alternative names: DNA-directed RNA polymerase II subunit D, RNA polymerase II 16 kDa subunit

All UniProt accessions (3): O15514, E9PB93, E9PHV4

UniProt curated annotations — full annotation on UniProt →

Function. Core component of RNA polymerase II (Pol II), a DNA-dependent RNA polymerase which synthesizes mRNA precursors and many functional non-coding RNAs using the four ribonucleoside triphosphates as substrates. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. POLR2D/RPB4 is part of a subcomplex with POLR2G/RPB7 that binds to a pocket formed by POLR2A/RPB1, POLR2B/RPB2 and POLR2F/RPABC2 at the base of the clamp element. The POLR2D/RPB4-POLR2G/RPB7 subcomplex seems to lock the clamp via POLR2G/RPB7 in the closed conformation thus preventing double-stranded DNA to enter the active site cleft. The POLR2D/RPB4-POLR2G/RPB7 subcomplex binds single-stranded DNA and RNA.

Subunit / interactions. Component of the RNA polymerase II (Pol II) core complex consisting of 12 subunits: a ten-subunit catalytic core composed of POLR2A/RPB1, POLR2B/RPB2, POLR2C/RPB3, POLR2I/RPB9, POLR2J/RPB11, POLR2E/RPABC1, POLR2F/RPABC2, POLR2H/RPABC3, POLR2K/RPABC4 and POLR2L/RPABC5 and a mobile stalk composed of two subunits POLR2D/RPB4 and POLR2G/RPB7, protruding from the core and functioning primarily in transcription initiation. Part of Pol II(G) complex, in which Pol II core associates with an additional subunit POLR2M; unlike conventional Pol II, Pol II(G) functions as a transcriptional repressor. Part of TBP-based Pol II pre-initiation complex (PIC), in which Pol II core assembles with general transcription factors and other specific initiation factors including GTF2E1, GTF2E2, GTF2F1, GTF2F2, TCEA1, ERCC2, ERCC3, GTF2H2, GTF2H3, GTF2H4, GTF2H5, GTF2A1, GTF2A2, GTF2B and TBP; this large multi-subunit PIC complex mediates DNA unwinding and targets Pol II core to the transcription start site where the first phosphodiester bond forms.

Subcellular location. Nucleus.

Similarity. Belongs to the eukaryotic RPB4 RNA polymerase subunit family.

RefSeq proteins (1): NP_004796* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005574	Rpb4/RPC9	Family
IPR006590	RNA_pol_Rpb4/RPC9_core	Domain
IPR010997	HRDC-like_sf	Homologous_superfamily
IPR038324	Rpb4/RPC9_sf	Homologous_superfamily
IPR045222	Rpb4-like	Family

Pfam: PF03874

UniProt features (11 total): helix 7, turn 2, chain 1, strand 1

Structure

Experimental structures (PDB)

22 structures.

PDB	Method	Resolution (Å)
9EHZ	ELECTRON MICROSCOPY	2.6
2C35	X-RAY DIFFRACTION	2.7
8XSO	ELECTRON MICROSCOPY	2.7
8XRM	ELECTRON MICROSCOPY	3.13
9EI1	ELECTRON MICROSCOPY	3.2
9EI3	ELECTRON MICROSCOPY	3.2
8XRJ	ELECTRON MICROSCOPY	3.6
9EI4	ELECTRON MICROSCOPY	3.7
5IYB	ELECTRON MICROSCOPY	3.9
5IYC	ELECTRON MICROSCOPY	3.9
5IYD	ELECTRON MICROSCOPY	3.9
6DRD	ELECTRON MICROSCOPY	3.9
8XVS	ELECTRON MICROSCOPY	4.1
6XRE	ELECTRON MICROSCOPY	4.6
9VD9	ELECTRON MICROSCOPY	4.6
7LBM	ELECTRON MICROSCOPY	4.8
5IYA	ELECTRON MICROSCOPY	5.4
5IY9	ELECTRON MICROSCOPY	6.3
5IY6	ELECTRON MICROSCOPY	7.2
6O9L	ELECTRON MICROSCOPY	7.2
5IY8	ELECTRON MICROSCOPY	7.9
5IY7	ELECTRON MICROSCOPY	8.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15514-F1	91.96	0.85

Function

Pathways and Gene Ontology

Reactome pathways

77 pathways

ID	Pathway
R-HSA-112382	Formation of RNA Pol II elongation complex
R-HSA-113418	Formation of the Early Elongation Complex
R-HSA-167152	Formation of HIV elongation complex in the absence of HIV Tat
R-HSA-167158	Formation of the HIV-1 Early Elongation Complex
R-HSA-167160	RNA Pol II CTD phosphorylation and interaction with CE during HIV infection
R-HSA-167161	HIV Transcription Initiation
R-HSA-167162	RNA Polymerase II HIV Promoter Escape
R-HSA-167172	Transcription of the HIV genome
R-HSA-167200	Formation of HIV-1 elongation complex containing HIV-1 Tat
R-HSA-167238	Pausing and recovery of Tat-mediated HIV elongation
R-HSA-167242	Abortive elongation of HIV-1 transcript in the absence of Tat
R-HSA-167243	Tat-mediated HIV elongation arrest and recovery
R-HSA-167246	Tat-mediated elongation of the HIV-1 transcript
R-HSA-167287	HIV elongation arrest and recovery
R-HSA-167290	Pausing and recovery of HIV elongation
R-HSA-168325	Viral Messenger RNA Synthesis
R-HSA-203927	MicroRNA (miRNA) biogenesis
R-HSA-5578749	Transcriptional regulation by small RNAs
R-HSA-5601884	PIWI-interacting RNA (piRNA) biogenesis
R-HSA-5617472	Activation of anterior HOX genes in hindbrain development during early embryogenesis
R-HSA-674695	RNA Polymerase II Pre-transcription Events
R-HSA-6781823	Formation of TC-NER Pre-Incision Complex
R-HSA-6781827	Transcription-Coupled Nucleotide Excision Repair (TC-NER)
R-HSA-6782135	Dual incision in TC-NER
R-HSA-6782210	Gap-filling DNA repair synthesis and ligation in TC-NER
R-HSA-6796648	TP53 Regulates Transcription of DNA Repair Genes
R-HSA-6803529	FGFR2 alternative splicing
R-HSA-6807505	RNA polymerase II transcribes snRNA genes
R-HSA-72086	mRNA Capping
R-HSA-72163	mRNA Splicing - Major Pathway

MSigDB gene sets: 209 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, REACTOME_VIRAL_MESSENGER_RNA_SYNTHESIS, REACTOME_SIGNALING_BY_FGFR, REACTOME_HIV_INFECTION, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GROSS_HYPOXIA_VIA_HIF1A_DN, KEGG_HUNTINGTONS_DISEASE, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_II_PROMOTER, MARZEC_IL2_SIGNALING_UP, REACTOME_MRNA_SPLICING, KEGG_PURINE_METABOLISM, DODD_NASOPHARYNGEAL_CARCINOMA_UP, GOCC_RNA_POLYMERASE_COMPLEX

GO Biological Process (3): transcription by RNA polymerase II (GO:0006366), transcription initiation at RNA polymerase II promoter (GO:0006367), DNA-templated transcription initiation (GO:0006352)

GO Molecular Function (3): nucleotide binding (GO:0000166), translation initiation factor binding (GO:0031369), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), RNA polymerase II, core complex (GO:0005665), cytosol (GO:0005829), nuclear speck (GO:0016607), DNA-directed RNA polymerase complex (GO:0000428), RNA polymerase complex (GO:0030880)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Transcription of the HIV genome	8
HIV Transcription Elongation	3
Gene Silencing by RNA	3
RNA Polymerase II Transcription Elongation	2
Late Phase of HIV Life Cycle	1
Tat-mediated elongation of the HIV-1 transcript	1
Influenza Viral RNA Transcription and Replication	1
Activation of HOX genes during differentiation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	2
cellular anatomical structure	2
DNA-templated transcription initiation	1
transcription by RNA polymerase II	1
RNA biosynthetic process	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
RNA polymerase II, holoenzyme	1
nuclear DNA-directed RNA polymerase complex	1
cytoplasm	1
nuclear ribonucleoprotein granule	1
RNA polymerase complex	1
transferase complex, transferring phosphorus-containing groups	1
intracellular protein-containing complex	1

Protein interactions and networks

STRING

2546 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POLR2D	POLR2G	P52433	999
POLR2D	POLR2C	P19387	982
POLR2D	POLR2A	P24928	980
POLR2D	POLR2F	P41584	972
POLR2D	POLR2B	P30876	963
POLR2D	POLR2L	P52436	950
POLR2D	POLR2I	P36954	937
POLR2D	POLR2E	P19388	933
POLR2D	POLR2K	P53803	922
POLR2D	POLR2J	P52435	866
POLR2D	POLR2H	P52434	845
POLR2D	SUPT5H	O00267	826
POLR2D	SUPT4H1	P63272	822
POLR2D	GTF2B	Q00403	806
POLR2D	POLR2J2	Q9GZM3	786

IntAct

125 interactions, top by confidence:

A	B	Type	Score
MED10	MED19	psi-mi:“MI:0914”(association)	0.910
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
MED29	MED19	psi-mi:“MI:0914”(association)	0.890
MED21	MED19	psi-mi:“MI:0914”(association)	0.880
MED11	MED19	psi-mi:“MI:0914”(association)	0.840
POLR2G	POLR2D	psi-mi:“MI:0914”(association)	0.840
POLR2L	POLR2D	psi-mi:“MI:0915”(physical association)	0.800
POLR2E	POLR2D	psi-mi:“MI:0915”(physical association)	0.790
MED9	MED19	psi-mi:“MI:0914”(association)	0.790
MED14	MED19	psi-mi:“MI:0914”(association)	0.790
POLR2D	MED19	psi-mi:“MI:0914”(association)	0.730
POLR2E	MED19	psi-mi:“MI:0914”(association)	0.730
RPRD1B	POLR2D	psi-mi:“MI:0914”(association)	0.730
MED19	MED19	psi-mi:“MI:0914”(association)	0.730
MED26	MED19	psi-mi:“MI:0914”(association)	0.730
MED21	POLR2D	psi-mi:“MI:0914”(association)	0.730
POLR2A	POLR2D	psi-mi:“MI:0914”(association)	0.730
POLR2C	POLR2D	psi-mi:“MI:0914”(association)	0.730
POLR2D	POLR2C	psi-mi:“MI:0914”(association)	0.730
POLR2J	POLR2D	psi-mi:“MI:0914”(association)	0.730
POLR2D	RECQL5	psi-mi:“MI:0914”(association)	0.640
MED10	POLR2D	psi-mi:“MI:0914”(association)	0.640
POLR2L	RCCD1	psi-mi:“MI:0914”(association)	0.640
POLR2F	POLR3A	psi-mi:“MI:0914”(association)	0.640

BioGRID (278): POLR2D (Co-localization), POLR2D (Co-localization), POLR2D (Co-localization), ESR1 (Co-localization), SRC (Co-localization), PSMB9 (Co-localization), POLR2D (Co-localization), TCEB3 (Co-localization), POLR2D (Affinity Capture-MS), POLR2D (Affinity Capture-MS), POLR2D (Affinity Capture-MS), POLR2D (Affinity Capture-MS), POLR2D (Affinity Capture-MS), ELP2 (Co-fractionation), MCFD2 (Co-fractionation)

ESM2 similar proteins: A1C928, A1D3P4, A1D9I5, A2R2E3, A4R4R3, B0XPV4, B8B624, E7EXT2, F7AEX0, O14617, O15514, O48534, O48890, O74825, P20433, P47076, P81128, P83509, Q0CU99, Q17MI0, Q1DM35, Q1JQ91, Q2KI89, Q2PIU8, Q2UBI2, Q3ZBC2, Q4W9M7, Q4WJ38, Q54S04, Q5AXH3, Q5R629, Q5RJU3, Q5TYV4, Q6DBA5, Q6GL75, Q6GLI9, Q6NU25, Q7XAM0, Q8CIM8, Q8WTJ4

Diamond homologs: O15514, O48890, O74825, P20433, Q1JQ91, Q54S04, Q9D7M8, Q9VEA5, Q6DBA5, Q7KSD8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
POLR2D	“form complex”	“RNA Polymerase II”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 98 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
FGFR2 mutant receptor activation	11	114.7×	9e-21
Signaling by FGFR2 IIIa TM	12	98.8×	2e-21
RNA Pol II CTD phosphorylation and interaction with CE during HIV infection	16	89.4×	6e-27
RNA Pol II CTD phosphorylation and interaction with CE	16	89.4×	6e-27
Abortive elongation of HIV-1 transcript in the absence of Tat	13	88.4×	5e-22
mRNA Capping	16	83.4×	2e-26
Pausing and recovery of Tat-mediated HIV elongation	14	70.7×	5e-22
Tat-mediated HIV elongation arrest and recovery	14	70.7×	5e-22

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of transcription elongation by RNA polymerase II	18	57.6×	4e-25
RNA polymerase II preinitiation complex assembly	17	49.2×	1e-22
positive regulation of transcription initiation by RNA polymerase II	17	49.2×	1e-22
transcription initiation at RNA polymerase II promoter	9	35.9×	3e-10
transcription elongation by RNA polymerase II	5	23.6×	1e-04
somatic stem cell population maintenance	6	15.8×	1e-04
transcription by RNA polymerase II	18	13.5×	1e-13
protein ubiquitination	14	6.2×	4e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

517 predictions. Top by Δscore:

Variant	Effect	Δscore
2:127850681:GCAAG:G	acceptor_gain	1.0000
2:127850682:CAAG:C	acceptor_gain	1.0000
2:127850682:CAAGC:C	acceptor_gain	1.0000
2:127850683:AAG:A	acceptor_gain	1.0000
2:127850684:AG:A	acceptor_gain	1.0000
2:127850686:C:A	acceptor_loss	1.0000
2:127850686:C:CC	acceptor_gain	1.0000
2:127850687:T:C	acceptor_loss	1.0000
2:127850691:C:CT	acceptor_gain	1.0000
2:127850692:A:T	acceptor_gain	1.0000
2:127848005:A:C	donor_gain	0.9900
2:127848112:A:AC	donor_gain	0.9900
2:127848113:C:CC	donor_gain	0.9900
2:127848181:CCAAG:C	acceptor_gain	0.9900
2:127848182:CAAGC:C	acceptor_gain	0.9900
2:127848186:C:CC	acceptor_gain	0.9900
2:127850586:TAA:T	donor_loss	0.9900
2:127850587:AACCT:A	donor_loss	0.9900
2:127850588:A:AC	donor_gain	0.9900
2:127850588:ACCT:A	donor_loss	0.9900
2:127850589:C:CC	donor_gain	0.9900
2:127850683:AAGCT:A	acceptor_gain	0.9900
2:127850684:AGCT:A	acceptor_gain	0.9900
2:127850685:GCTAA:G	acceptor_gain	0.9900
2:127850686:CT:C	acceptor_gain	0.9900
2:127853104:CT:C	acceptor_gain	0.9900
2:127853110:T:C	acceptor_gain	0.9900
2:127853110:T:TC	acceptor_gain	0.9900
2:127857922:G:A	donor_gain	0.9900
2:127858054:T:TA	donor_gain	0.9900

AlphaMissense

941 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:127850634:G:C	N102K	1.000
2:127850634:G:T	N102K	1.000
2:127853048:C:G	R44P	1.000
2:127853060:A:G	L40P	1.000
2:127853084:A:T	L32H	1.000
2:127848123:C:G	R138P	0.999
2:127848144:A:G	L131P	0.999
2:127848156:A:G	L127P	0.999
2:127850599:A:G	L114P	0.999
2:127850626:G:T	P105Q	0.999
2:127850632:A:G	L103P	0.999
2:127850638:G:T	A101D	0.999
2:127850647:G:T	A98D	0.999
2:127850653:T:A	E96V	0.999
2:127850654:C:T	E96K	0.999
2:127850655:A:C	F95L	0.999
2:127850655:A:T	F95L	0.999
2:127850657:A:G	F95L	0.999
2:127850680:A:G	L87P	0.999
2:127852928:C:G	R84P	0.999
2:127852929:G:T	R84S	0.999
2:127852931:A:T	V83D	0.999
2:127852958:A:G	F74S	0.999
2:127852988:G:T	T64K	0.999
2:127852996:G:C	F61L	0.999
2:127852996:G:T	F61L	0.999
2:127852998:A:G	F61L	0.999
2:127853039:T:G	Q47P	0.999
2:127853057:A:G	L41P	0.999
2:127853057:A:T	L41Q	0.999

dbSNP variants (sampled 300 via entrez): RS1000244064 (2:127843422 A>G), RS1000294670 (2:127843665 G>A), RS1000311521 (2:127856292 A>G), RS1000320983 (2:127856475 A>C), RS1000587245 (2:127850355 G>A), RS1000884652 (2:127844891 T>C), RS1001195528 (2:127856583 T>A), RS1001205437 (2:127856926 C>G,T), RS1001326584 (2:127845542 A>G), RS1001511667 (2:127844222 G>C,T), RS1001608730 (2:127851065 A>G), RS1001701719 (2:127843817 A>T), RS1001742231 (2:127851042 G>A), RS1001753986 (2:127843964 C>A), RS1001956660 (2:127855415 A>AG)

Disease associations

OMIM: gene MIM:606017 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST010241_360	Apolipoprotein A1 levels	6.000000e-11
GCST010242_158	HDL cholesterol levels	8.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression	2
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
sodium arsenite	decreases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
CGP 52608	increases reaction, affects binding	1
ICG 001	decreases expression	1
Zoledronic Acid	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Coumestrol	increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Nickel	increases expression	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Valproic Acid	affects expression	1
Aflatoxin B1	increases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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