CRCP

Summary

CRCP (CGRP receptor component, HGNC:17888) is a protein-coding gene on chromosome 7q11.21, encoding DNA-directed RNA polymerase III subunit RPC9 (O75575). DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. It is a common-essential gene (DepMap: required in 98.4% of cancer cell lines).

This gene encodes a membrane protein that functions as part of a receptor complex for a small neuropeptide that increases intracellular cAMP levels. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.

Source: NCBI Gene 27297 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 36 total
• Cancer dependency (DepMap): dependent in 98.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_014478

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17888
Approved symbol	CRCP
Name	CGRP receptor component
Location	7q11.21
Locus type	gene with protein product
Status	Approved
Aliases	CGRP-RCP, RCP, RCP9, C17, POLR3I
Ensembl gene	ENSG00000241258
Ensembl biotype	protein_coding
OMIM	606121
Entrez	27297

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 8 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000338592, ENST00000360415, ENST00000395326, ENST00000398684, ENST00000431089, ENST00000486848, ENST00000492264, ENST00000718079, ENST00000718080, ENST00000870873, ENST00000936880, ENST00000936881

RefSeq mRNA: 4 — MANE Select: NM_014478 NM_001040647, NM_001040648, NM_001142414, NM_014478

CCDS: CCDS47599, CCDS47600, CCDS55116, CCDS5532

Canonical transcript exons

ENST00000395326 — 6 exons

Exon	Start	End
ENSE00001927708	66114847	66114970
ENSE00003489373	66134280	66134374
ENSE00003535356	66127704	66127740
ENSE00003562900	66130744	66130842
ENSE00003620949	66145443	66145500
ENSE00004034064	66152208	66154568

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 92.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.8612 / max 175.6751, expressed in 1824 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
78854	24.2491	1821
78855	8.3699	1746
78856	0.2422	94

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	92.18	gold quality
ganglionic eminence	UBERON:0004023	91.32	gold quality
cortical plate	UBERON:0005343	90.45	gold quality
islet of Langerhans	UBERON:0000006	89.16	gold quality
adrenal tissue	UBERON:0018303	88.85	gold quality
right lobe of liver	UBERON:0001114	88.69	gold quality
monocyte	CL:0000576	88.38	gold quality
oocyte	CL:0000023	88.03	gold quality
mononuclear cell	CL:0000842	87.97	gold quality
leukocyte	CL:0000738	87.85	gold quality
rectum	UBERON:0001052	87.74	gold quality
amniotic fluid	UBERON:0000173	87.07	gold quality
stromal cell of endometrium	CL:0002255	86.95	gold quality
prefrontal cortex	UBERON:0000451	86.84	gold quality
colonic epithelium	UBERON:0000397	86.45	gold quality
ventricular zone	UBERON:0003053	86.30	gold quality
secondary oocyte	CL:0000655	86.10	gold quality
adrenal gland	UBERON:0002369	86.05	gold quality
left adrenal gland	UBERON:0001234	85.78	gold quality
pancreas	UBERON:0001264	85.75	gold quality
popliteal artery	UBERON:0002250	85.69	gold quality
tibial artery	UBERON:0007610	85.68	gold quality
right adrenal gland	UBERON:0001233	85.57	gold quality
sural nerve	UBERON:0015488	85.46	gold quality
left adrenal gland cortex	UBERON:0035825	85.21	gold quality
anterior cingulate cortex	UBERON:0009835	85.17	gold quality
cingulate cortex	UBERON:0003027	85.08	gold quality
stomach	UBERON:0000945	85.04	gold quality
body of stomach	UBERON:0001161	84.97	gold quality
mucosa of transverse colon	UBERON:0004991	84.93	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.79
E-GEOD-100618	no	121.48
E-GEOD-99795	no	64.78

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2

miRNA regulators (miRDB)

69 targeting CRCP, 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-3613-3P	100.00	76.36	7965
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-18A-3P	99.56	65.68	1092
HSA-MIR-6083	99.47	68.73	2393

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 14)

• Expression of CGRP-RCP was detected in CD34+ cells and also in some mature granulocyte samples, providing evidence that CGRP-RCP may be regulated independently of RAMP1 and CRLR in hematopoietic cells. (PMID:11937264)
• human CGRP-RCP is the genuine orthologue of C17. CGRP-RCP was found to functionally replace C17 in Deltarpc17 yeast cells; CGRP-RCP was identified in a purified human Pol III preparation. (PMID:12482973)
• inhibition of ACE seems to augment CGRP catabolism. (PMID:16406141)
• Increased mRNA expression CGRP-RCP in gravid myometrium supports the possibility of involvement of CGRP in the control of myometrial contractility. (PMID:17853344)
• A peptide mimetic demonstrates that 12 residues of family B member CGRP receptor proximal C-terminus are required for this receptor’s expression and localization at the cell membrane. (PMID:18636754)
• analysis of the effects of antagonists to the CGRP receptor (PMID:19053766)
• Data describe the role of residues 23-60 of the calcitonin receptor-like receptor in binding with interaction sites within the N-terminus of the calcitonin gene-related peptide receptor. (PMID:19913063)
• The extracellular protein domains corresponding to residues 23-133 of calcitonin receptor-like receptor and residues 26-117 of receptor activity-modifying protein 1 (RAMP1) are shown to be sufficient for formation of a stable, folded monodisperse complex. (PMID:20099900)
• This study demonstrates the detailed expression of CGRP and its receptor components within spinal trigeminal nucleus in the brainstem and in the spinal cord at C1-level (PMID:22074408)
• In this review, the influence of the CGRP family peptides in reproduction and pregnancy is explored and discussed. (PMID:25015815)
• data reinforce and clarify our understanding of CGRP receptor localization, and provide evidence that antagonist antibodies bind to target sites in the trigeminovascular system of primates that are involved in the pathology of migraine (PMID:27155150)
• CGRP family of receptors displays both ligand- and RAMP-dependent signaling bias among the Galphas, Galphai, and Galphaq/11 pathways. (PMID:27566546)
• both anti-CGRP and anti-CGRP receptor monoclonal antibodies (mABs) completed clinical development, and the first representatives of these 2 classes are available on the market. MABs are approved for prevention of migraine attacks in chronic or episodic migraine, involving long-term treatments. (PMID:31018157)
• Meningeal lymphatic CGRP signaling governs pain via cerebrospinal fluid efflux and neuroinflammation in migraine models. (PMID:38743922)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	crcp	ENSDARG00000069373
mus_musculus	Crcp	ENSMUSG00000025532
rattus_norvegicus	Crcp	ENSRNOG00000071267
drosophila_melanogaster	Polr3I	FBGN0030801
caenorhabditis_elegans		WBGENE00044924

Protein

Protein identifiers

DNA-directed RNA polymerase III subunit RPC9 — O75575 (reviewed: O75575)

Alternative names: Calcitonin gene-related peptide-receptor component protein

All UniProt accessions (2): O75575, H7BY40

UniProt curated annotations — full annotation on UniProt →

Function. DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Specific peripheric component of RNA polymerase III (Pol III) which synthesizes small non-coding RNAs including 5S rRNA, snRNAs, tRNAs and miRNAs from at least 500 distinct genomic loci. With POLR3H/RPC8 forms a mobile stalk that protrudes from Pol III core and functions primarily in transcription initiation. Pol III plays a key role in sensing and limiting infection by intracellular bacteria and DNA viruses. Acts as nuclear and cytosolic DNA sensor involved in innate immune response. Can sense non-self dsDNA that serves as template for transcription into dsRNA. The non-self RNA polymerase III transcripts, such as Epstein-Barr virus-encoded RNAs (EBERs) induce type I interferon and NF-kappa-B through the RIG-I pathway. Accessory protein for the calcitonin gene-related peptide (CGRP) receptor. It modulates CGRP responsiveness in a variety of tissues.

Subunit / interactions. Component of the RNA polymerase III complex consisting of 17 subunits: a ten-subunit horseshoe-shaped catalytic core composed of POLR3A/RPC1, POLR3B/RPC2, POLR1C/RPAC1, POLR1D/RPAC2, POLR3K/RPC10, POLR2E/RPABC1, POLR2F/RPABC2, POLR2H/RPABC3, POLR2K/RPABC4 and POLR2L/RPABC5; a mobile stalk composed of two subunits POLR3H/RPC8 and CRCP/RPC9, protruding from the core and functioning primarily in transcription initiation; and additional subunits homologous to general transcription factors of the RNA polymerase II machinery, POLR3C/RPC3-POLR3F/RPC6-POLR3G/RPC7 heterotrimer required for transcription initiation and POLR3D/RPC4-POLR3E/RPC5 heterodimer involved in both transcription initiation and termination.

Subcellular location. Nucleus. Cell membrane.

Tissue specificity. Ubiquitous. Most prevalent in testis.

Similarity. Belongs to the eukaryotic RPC9 RNA polymerase subunit family.

Isoforms (4)

UniProt ID	Names	Canonical?
O75575-1	1	yes
O75575-2	2
O75575-3	3
O75575-4	4

RefSeq proteins (4): NP_001035737, NP_001035738, NP_001135886, NP_055293* (*=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
IPR038846	RPC9	Family

Pfam: PF03874

UniProt features (18 total): helix 8, strand 4, splice variant 3, chain 1, region of interest 1, turn 1

Structure

Experimental structures (PDB)

29 structures.

PDB	Method	Resolution (Å)
7AE1	ELECTRON MICROSCOPY	2.8
9K39	ELECTRON MICROSCOPY	2.8
7D58	ELECTRON MICROSCOPY	2.9
9K36	ELECTRON MICROSCOPY	2.9
9K2G	ELECTRON MICROSCOPY	3
9K3U	ELECTRON MICROSCOPY	3
7AE3	ELECTRON MICROSCOPY	3.1
7D59	ELECTRON MICROSCOPY	3.1
9K38	ELECTRON MICROSCOPY	3.1
9FSO	ELECTRON MICROSCOPY	3.28
7A6H	ELECTRON MICROSCOPY	3.3
9LXN	ELECTRON MICROSCOPY	3.3
7DU2	ELECTRON MICROSCOPY	3.35
9FSP	ELECTRON MICROSCOPY	3.39
7AEA	ELECTRON MICROSCOPY	3.4
8IUH	ELECTRON MICROSCOPY	3.4
7DN3	ELECTRON MICROSCOPY	3.5
9K3V	ELECTRON MICROSCOPY	3.5
9LKT	ELECTRON MICROSCOPY	3.5
9FSQ	ELECTRON MICROSCOPY	3.51
7FJI	ELECTRON MICROSCOPY	3.6
7FJJ	ELECTRON MICROSCOPY	3.6
9LXO	ELECTRON MICROSCOPY	3.6
9FSR	ELECTRON MICROSCOPY	3.76
8ITY	ELECTRON MICROSCOPY	3.9
7AST	ELECTRON MICROSCOPY	4
8IUE	ELECTRON MICROSCOPY	4.1
9FSS	ELECTRON MICROSCOPY	4.14
9K3B	ELECTRON MICROSCOPY	4.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75575-F1	83.31	0.59

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-1834949	Cytosolic sensors of pathogen-associated DNA
R-HSA-73780	RNA Polymerase III Chain Elongation
R-HSA-73980	RNA Polymerase III Transcription Termination
R-HSA-749476	RNA Polymerase III Abortive And Retractive Initiation
R-HSA-76061	RNA Polymerase III Transcription Initiation From Type 1 Promoter
R-HSA-76066	RNA Polymerase III Transcription Initiation From Type 2 Promoter
R-HSA-76071	RNA Polymerase III Transcription Initiation From Type 3 Promoter
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-74158	RNA Polymerase III Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-76046	RNA Polymerase III Transcription Initiation

MSigDB gene sets: 151 (showing top): MORF_RAGE, REACTOME_RNA_POLYMERASE_III_TRANSCRIPTION_INITIATION_FROM_TYPE_3_PROMOTER, REACTOME_RNA_POLYMERASE_III_TRANSCRIPTION_TERMINATION, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_RNA_POLYMERASE_III_CHAIN_ELONGATION, GOBP_DNA_TEMPLATED_TRANSCRIPTION_TERMINATION, GOCC_SECRETORY_GRANULE, GOBP_TRANSCRIPTION_BY_RNA_POLYMERASE_III, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, MODULE_379, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_DEFENSE_RESPONSE_TO_VIRUS, GOMF_PEPTIDE_RECEPTOR_ACTIVITY, MORF_PML, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_UP

GO Biological Process (7): transcription by RNA polymerase III (GO:0006383), transcription initiation at RNA polymerase III promoter (GO:0006384), neuropeptide signaling pathway (GO:0007218), innate immune response (GO:0045087), defense response to virus (GO:0051607), immune system process (GO:0002376), DNA-templated transcription initiation (GO:0006352)

GO Molecular Function (4): nucleotide binding (GO:0000166), calcitonin gene-related peptide receptor activity (GO:0001635), DNA-directed RNA polymerase activity (GO:0003899), protein binding (GO:0005515)

GO Cellular Component (10): acrosomal vesicle (GO:0001669), nucleoplasm (GO:0005654), RNA polymerase III complex (GO:0005666), cytosol (GO:0005829), plasma membrane (GO:0005886), DNA polymerase III complex (GO:0009360), DNA-directed RNA polymerase complex (GO:0000428), nucleus (GO:0005634), membrane (GO:0016020), RNA polymerase complex (GO:0030880)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
RNA Polymerase III Transcription	4
RNA Polymerase III Transcription Initiation	3
Innate Immune System	1
Immune System	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
DNA-templated transcription	2
RNA biosynthetic process	2
DNA-templated transcription initiation	1
transcription by RNA polymerase III	1
G protein-coupled receptor signaling pathway	1
immune response	1
defense response to symbiont	1
defense response	1
response to virus	1
biological_process	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
calcitonin family receptor activity	1
5’-3’ RNA polymerase activity	1
binding	1
secretory granule	1
nuclear lumen	1
DNA-directed RNA polymerase complex	1
nuclear protein-containing complex	1
cytoplasm	1
membrane	1
cell periphery	1
DNA polymerase complex	1
RNA polymerase complex	1
intracellular membrane-bounded organelle	1
transferase complex, transferring phosphorus-containing groups	1
intracellular protein-containing complex	1

Protein interactions and networks

STRING

1202 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRCP	RAMP1	O60894	981
CRCP	CALCRL	Q16602	980
CRCP	ADM	P35318	819
CRCP	POLR3H	Q9Y535	800
CRCP	POLR3F	Q9H1D9	796
CRCP	POLR3C	Q9BUI4	775
CRCP	POLR3G	O15318	772
CRCP	POLR3E	Q9NVU0	711
CRCP	POLR3D	P05423	666
CRCP	POLR1C	O15160	626
CRCP	POLR3B	Q9NW08	609
CRCP	POLR1D	P0DPB6	605
CRCP	POLR2L	P52436	589
CRCP	POLR2E	P19388	574
CRCP	POLR2H	P52434	571

IntAct

73 interactions, top by confidence:

A	B	Type	Score
POLR2E	POLR3A	psi-mi:“MI:0915”(physical association)	0.870
POLR3GL	POLR3A	psi-mi:“MI:0914”(association)	0.730
POLR2E	MED19	psi-mi:“MI:0914”(association)	0.730
POLR3E	POLR3A	psi-mi:“MI:0914”(association)	0.730
POLR3D	POLR3A	psi-mi:“MI:0914”(association)	0.640
POLR2L	RCCD1	psi-mi:“MI:0914”(association)	0.640
POLR3K	POLR3A	psi-mi:“MI:0914”(association)	0.640
POLR2F	POLR3A	psi-mi:“MI:0914”(association)	0.640
POLR2L	POLR3A	psi-mi:“MI:0914”(association)	0.640
CRCP	ZMIZ2	psi-mi:“MI:0915”(physical association)	0.560
TCF12	CRCP	psi-mi:“MI:0915”(physical association)	0.560
ZMIZ2	CRCP	psi-mi:“MI:0915”(physical association)	0.560
CRCP	TCF12	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (138): CRCP (Two-hybrid), ZMIZ2 (Two-hybrid), CRCP (Affinity Capture-RNA), CRCP (Affinity Capture-RNA), CRCP (Affinity Capture-RNA), CRCP (Affinity Capture-MS), CRCP (Co-fractionation), CRCP (Co-fractionation), CRCP (Co-fractionation), CRCP (Co-fractionation), CRCP (Co-fractionation), CRCP (Co-fractionation), CRCP (Co-fractionation), CRCP (Co-fractionation), CRCP (Co-fractionation)

ESM2 similar proteins: A0JN61, A4QNE0, O35427, O60763, O60941, O70585, O75575, O88597, O95453, P11029, P11497, P13984, P41541, P41542, P69341, Q01750, Q05B58, Q0JNK5, Q13085, Q13901, Q14457, Q28559, Q2T9L9, Q32PE4, Q3ZBJ0, Q4A1L4, Q4A1L5, Q5R4J9, Q5R660, Q5R878, Q5RBU4, Q5SWU9, Q5ZHS3, Q5ZKS6, Q60482, Q6NRL4, Q80UM3, Q8BWQ6, Q8L5Y9, Q8NE86

Diamond homologs: A0JN61, O35427, O75575, Q60482, Q8VHM6, Q9C0Z9, P47076

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CRCP	“form complex”	“RNA Polymerase III”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 39 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
RNA Polymerase III Chain Elongation	17	371.9×	2e-44
RNA Polymerase III Transcription Termination	17	291.1×	7e-41
RNA Polymerase III Transcription Initiation From Type 2 Promoter	19	277.1×	1e-44
RNA Polymerase III Transcription Initiation From Type 1 Promoter	19	267.2×	1e-44
RNA Polymerase III Transcription Initiation From Type 3 Promoter	19	267.2×	1e-44
RNA Polymerase III Transcription Initiation	19	220.1×	2e-42
RNA Polymerase III Transcription	19	213.8×	3e-42
RNA Polymerase III Abortive And Retractive Initiation	19	182.5×	2e-40

GO biological processes:

GO term	Partners	Fold	FDR
transcription by RNA polymerase III	8	170.2×	1e-14
positive regulation of innate immune response	5	73.1×	2e-07
positive regulation of interferon-beta production	6	65.3×	2e-08
defense response to virus	9	17.3×	7e-08
transcription by RNA polymerase II	6	11.8×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1346 predictions. Top by Δscore:

Variant	Effect	Δscore
7:66114966:G:GT	donor_gain	1.0000
7:66114969:GT:G	donor_gain	1.0000
7:66127698:TTTCA:T	acceptor_loss	1.0000
7:66127699:TTCA:T	acceptor_loss	1.0000
7:66127701:CA:C	acceptor_loss	1.0000
7:66127702:A:AG	acceptor_gain	1.0000
7:66127702:A:C	acceptor_loss	1.0000
7:66127702:A:G	acceptor_loss	1.0000
7:66127703:G:A	acceptor_loss	1.0000
7:66127703:G:GG	acceptor_gain	1.0000
7:66127703:GGAA:G	acceptor_gain	1.0000
7:66130740:CTA:C	acceptor_loss	1.0000
7:66130741:TA:T	acceptor_loss	1.0000
7:66130741:TAG:T	acceptor_loss	1.0000
7:66130742:A:AC	acceptor_loss	1.0000
7:66130840:G:GT	donor_gain	1.0000
7:66130840:GAA:G	donor_gain	1.0000
7:66130843:G:GG	donor_gain	1.0000
7:66145497:GCTG:G	donor_gain	1.0000
7:66145498:CTGGT:C	donor_loss	1.0000
7:66145499:TGGTG:T	donor_loss	1.0000
7:66145500:GGTG:G	donor_loss	1.0000
7:66145501:G:GA	donor_loss	1.0000
7:66145502:T:A	donor_loss	1.0000
7:66145502:T:TC	donor_loss	1.0000
7:66145503:GAGT:G	donor_loss	1.0000
7:66152204:GCAG:G	acceptor_loss	1.0000
7:66152205:CA:C	acceptor_loss	1.0000
7:66152206:A:AG	acceptor_gain	1.0000
7:66152206:AGAT:A	acceptor_gain	1.0000

AlphaMissense

982 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:66145454:T:C	L84P	0.999
7:66145460:T:C	L86P	0.998
7:66145467:C:A	N88K	0.998
7:66145467:C:G	N88K	0.998
7:66127729:A:C	S12R	0.997
7:66127731:T:A	S12R	0.997
7:66127731:T:G	S12R	0.997
7:66130757:T:C	L20P	0.997
7:66130832:T:A	I45N	0.997
7:66134368:T:C	L78S	0.997
7:66145448:A:T	E82V	0.997
7:66145463:T:C	L87P	0.997
7:66145449:G:C	E82D	0.996
7:66145449:G:T	E82D	0.996
7:66145475:C:A	P91H	0.996
7:66152230:G:C	R107P	0.996
7:66152233:T:C	L108P	0.996
7:66152257:T:C	L116P	0.996
7:66127734:C:A	N13K	0.995
7:66127734:C:G	N13K	0.995
7:66145460:T:G	L86R	0.995
7:66145475:C:G	P91R	0.995
7:66145499:T:C	L99P	0.995
7:66130832:T:G	I45S	0.994
7:66130837:T:G	Y47D	0.994
7:66134281:C:A	T49K	0.994
7:66145447:G:A	E82K	0.994
7:66134280:A:C	T49P	0.993
7:66127727:T:A	L11H	0.992
7:66134344:T:C	L70P	0.992

dbSNP variants (sampled 300 via entrez): RS1000034769 (7:66141518 A>G,T), RS1000148937 (7:66141762 A>G), RS1000259510 (7:66135299 C>T), RS1000321287 (7:66118692 T>C), RS1000534551 (7:66149807 A>G), RS1000546758 (7:66126214 G>C), RS1000658315 (7:66119816 A>G), RS1000772386 (7:66130351 A>C,G,T), RS1000777703 (7:66135653 C>T), RS1000966555 (7:66149014 A>C), RS1001073439 (7:66114443 G>A,C), RS1001078481 (7:66119088 G>C), RS1001134987 (7:66142475 G>C,T), RS1001160655 (7:66140588 C>G), RS1001199047 (7:66131051 T>C)

Disease associations

OMIM: gene MIM:606121 | 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
GCST000943_3	Aortic root size	4.000000e-06
GCST008059_250	Estimated glomerular filtration rate	3.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1976200	CRCP		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects methylation, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
geldanamycin	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation, affects cotreatment	1
sodium arsenate	increases abundance, increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
bisphenol S	decreases methylation	1
jinfukang	affects cotreatment, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Vorinostat	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects methylation, increases abundance	1
Cisplatin	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects expression	1
Hydrogen Peroxide	affects expression	1
Methotrexate	decreases expression	1
Nitrogen Dioxide	affects methylation, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Thimerosal	decreases expression	1
Thiram	increases expression	1
Cyclosporine	increases expression	1
Asbestos, Crocidolite	decreases expression	1

Clinical trials (associated diseases)

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