CR1L

Summary

CR1L (complement C3b/C4b receptor 1 like, HGNC:2335) is a protein-coding gene on chromosome 1q32.2, encoding Complement component receptor 1-like protein (Q2VPA4). It is a selective cancer dependency (DepMap: 13.6% of cell lines).

Acts upstream of or within regulation of complement activation and regulation of complement-dependent cytotoxicity. Part of receptor complex.

Source: NCBI Gene 1379 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 113 total
• Cancer dependency (DepMap): dependent in 13.6% of screened cell lines
• MANE Select transcript: NM_175710

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2335
Approved symbol	CR1L
Name	complement C3b/C4b receptor 1 like
Location	1q32.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000197721
Ensembl biotype	protein_coding
OMIM	605886
Entrez	1379

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 protein_coding, 1 retained_intron

ENST00000294997, ENST00000430248, ENST00000508064, ENST00000530905, ENST00000531844

RefSeq mRNA: 1 — MANE Select: NM_175710 NM_175710

CCDS: CCDS44310

Canonical transcript exons

ENST00000508064 — 12 exons

Exon	Start	End
ENSE00002061345	207723618	207723703
ENSE00002154491	207645133	207645330
ENSE00002354300	207697503	207697679
ENSE00002361643	207694353	207694751
ENSE00002382227	207699189	207699274
ENSE00002400062	207708178	207708263
ENSE00002410911	207701519	207701618
ENSE00002415560	207697771	207697873
ENSE00003474500	207683872	207683957
ENSE00003528073	207677389	207677568
ENSE00003593912	207717464	207717691
ENSE00003630109	207678198	207678297

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 83.35.

FANTOM5 (CAGE): breadth broad, TPM avg 5.3815 / max 521.2141, expressed in 188 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
8256	5.2190	186
201929	0.1625	69

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow	UBERON:0002371	83.35	gold quality
trabecular bone tissue	UBERON:0002483	80.90	gold quality
bone marrow cell	CL:0002092	78.57	gold quality
blood	UBERON:0000178	76.83	gold quality
monocyte	CL:0000576	74.18	gold quality
leukocyte	CL:0000738	72.44	gold quality
lymph node	UBERON:0000029	68.98	gold quality
vermiform appendix	UBERON:0001154	66.04	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	64.60	gold quality
spleen	UBERON:0002106	63.63	gold quality
buccal mucosa cell	CL:0002336	63.33	gold quality
right uterine tube	UBERON:0001302	62.52	gold quality
metanephros cortex	UBERON:0010533	61.15	gold quality
caecum	UBERON:0001153	60.44	gold quality
secondary oocyte	CL:0000655	59.43	gold quality
cortex of kidney	UBERON:0001225	57.77	gold quality
right lung	UBERON:0002167	57.41	gold quality
adult mammalian kidney	UBERON:0000082	56.20	gold quality
cartilage tissue	UBERON:0002418	56.09	gold quality
metanephros	UBERON:0000081	54.98	gold quality
liver	UBERON:0002107	52.96	gold quality
right lobe of liver	UBERON:0001114	52.29	gold quality
nasal cavity mucosa	UBERON:0001826	52.19	gold quality
adrenal tissue	UBERON:0018303	52.06	gold quality
placenta	UBERON:0001987	51.84	gold quality
colonic epithelium	UBERON:0000397	51.78	silver quality
tonsil	UBERON:0002372	51.30	gold quality
kidney	UBERON:0002113	51.15	gold quality
oocyte	CL:0000023	49.70	silver quality
fallopian tube	UBERON:0003889	49.39	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	37.57
E-ANND-3	yes	5.02
E-MTAB-9067	yes	4.81
E-HCAD-10	no	2.27

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 13.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• CR1L transcript appears to be limited to hematopoietic and fetal lymphoid tissue. (PMID:14687939)

Cross-species orthologs

0 orthologs

Paralogs (39): CFH (ENSG00000000971), SELE (ENSG00000007908), C8B (ENSG00000021852), C6 (ENSG00000039537), SEZ6 (ENSG00000063015), CFHR2 (ENSG00000080910), APOH (ENSG00000091583), SEZ6L (ENSG00000100095), SUSD6 (ENSG00000100647), SRPX (ENSG00000101955), SRPX2 (ENSG00000102359), C7 (ENSG00000112936), C9 (ENSG00000113600), PAPPA2 (ENSG00000116183), CFHR3 (ENSG00000116785), CR2 (ENSG00000117322), CD46 (ENSG00000117335), CSMD2 (ENSG00000121904), C4BPA (ENSG00000123838), C4BPB (ENSG00000123843), CFHR4 (ENSG00000134365), CFHR5 (ENSG00000134389), F13B (ENSG00000143278), SUSD4 (ENSG00000143502), C8A (ENSG00000157131), SUSD3 (ENSG00000157303), CSMD3 (ENSG00000164796), SVEP1 (ENSG00000165124), C2 (ENSG00000166278), SELP (ENSG00000174175), SEZ6L2 (ENSG00000174938), PRF1 (ENSG00000180644), PAPPA (ENSG00000182752), CSMD1 (ENSG00000183117), SELL (ENSG00000188404), CD55 (ENSG00000196352), CR1 (ENSG00000203710), CFB (ENSG00000243649), CFHR1 (ENSG00000244414)

Protein

Protein identifiers

Complement component receptor 1-like protein — Q2VPA4 (reviewed: Q2VPA4)

Alternative names: Complement C4b-binding protein CR-1-like protein

All UniProt accessions (2): A0A0C4DGF5, Q2VPA4

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with iC4 (methylamine-treated C4) but not for iC3 (methylamine-treated C3).

Subcellular location. Cytoplasm. Membrane. Secreted.

Tissue specificity. Expressed in fetal liver and to a lesser extent in fetal spleen and thymus. Expression appears to be limited to hematopoietic and fetal lymphoid tissue.

Similarity. Belongs to the receptors of complement activation (RCA) family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q2VPA4-1	1	yes
Q2VPA4-2	2
Q2VPA4-3	3

RefSeq proteins (1): NP_783641* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000436	Sushi_SCR_CCP_dom	Domain
IPR035976	Sushi/SCR/CCP_sf	Homologous_superfamily
IPR050350	Compl-Cell_Adhes-Reg	Family

Pfam: PF00084

UniProt features (34 total): disulfide bond 15, domain 8, sequence variant 5, splice variant 3, signal peptide 1, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2VPA4-F1	83.25	0.50

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (15): 35–78, 65–91, 96–137, 123–153, 158–207, 187–224, 230–272, 258–285, 289–332, 318–345, 350–392, 378–408, 413–454, 440–470, 504–541

Glycosylation sites (1): 48

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 108 (showing top): GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_MEDIATED_IMMUNITY, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_B_CELL_MEDIATED_IMMUNITY, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_COMPLEMENT_ACTIVATION, GOBP_LYMPHOCYTE_MEDIATED_IMMUNITY, GOBP_REGULATION_OF_B_CELL_MEDIATED_IMMUNITY, GOBP_REGULATION_OF_LYMPHOCYTE_MEDIATED_IMMUNITY, GOBP_HUMORAL_IMMUNE_RESPONSE, GOBP_ADAPTIVE_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_HUMORAL_IMMUNE_RESPONSE, GOBP_REGULATION_OF_LEUKOCYTE_MEDIATED_IMMUNITY

GO Biological Process (4): T cell mediated immunity (GO:0002456), regulation of complement activation (GO:0030449), negative regulation of complement activation, classical pathway (GO:0045959), regulation of complement-dependent cytotoxicity (GO:1903659)

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

GO Cellular Component (6): obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), plasma membrane (GO:0005886), signaling receptor complex (GO:0043235), extracellular region (GO:0005576), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
lymphocyte mediated immunity	1
adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	1
regulation of immune effector process	1
regulation of humoral immune response	1
complement activation	1
negative regulation of humoral immune response mediated by circulating immunoglobulin	1
complement activation, classical pathway	1
regulation of complement activation, classical pathway	1
negative regulation of complement activation	1
regulation of cell killing	1
complement-dependent cytotoxicity	1
binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
protein-containing complex	1

Protein interactions and networks

STRING

484 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CR1L	C4A	P01028	737
CR1L	CLU	P10909	727
CR1L	C3	P01024	675
CR1L	ABCA7	Q8IZY2	626
CR1L	PICALM	Q13492	624
CR1L	C4A	P01028	570
CR1L	BIN1	O00499	479
CR1L	EXOC3L2	Q2M3D2	444
CR1L	SORL1	Q92673	439
CR1L	APOE	P02649	434
CR1L	ATP12A	P54707	432
CR1L	PSEN2	P49810	432
CR1L	CFH	P08603	428
CR1L	MAPT	P10636	424
CR1L	CD2AP	Q9Y5K6	400

IntAct

5 interactions, top by confidence:

A	B	Type	Score
CR1L	DDHD1	psi-mi:“MI:0915”(physical association)	0.560
CR1L	ACTL6B	psi-mi:“MI:0914”(association)	0.350
CR1L	DDHD1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (8): CR1L (Two-hybrid), ACTA2 (Affinity Capture-MS), ACTL6B (Affinity Capture-MS), NFYC (Affinity Capture-MS), CR1 (Affinity Capture-MS), SERPINB8 (Affinity Capture-MS), RMND1 (Affinity Capture-MS), CR1L (Affinity Capture-MS)

ESM2 similar proteins: O02839, O08569, O19124, O62685, O62837, O88174, P02749, P04003, P05160, P08607, P14151, P15529, P16109, P17690, P19070, P20023, P26644, P27113, P30836, P42201, P49457, P70105, P79138, P98107, P98109, P98131, Q01102, Q03472, Q07968, Q28065, Q28768, Q2VPA4, Q5R4D0, Q60401, Q60736, Q61475, Q61476, Q63135, Q63514, Q64735

Diamond homologs: A0A1D5NSM8, B5DF94, O60687, P08607, P0C6B8, P42201, P78539, P98109, Q2VPA4, Q3SYW2, Q5EA25, Q63769, Q6GP28, Q6QD51, Q76M96, Q8R054, Q8R2G6, Q9R0M3, A2AR95, A2ARV4, A2AVA0, A4IHY6, A7MBS7, B3EWY9, B3EWZ3, C0HL12, C5IAW9, D3YXF5, D3YXG0, D3ZTD8, E9Q6D8, F1LW30, O08721, O08722, O14514, O15072, O60241, O60242, O75074, O88307

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	97
Likely benign	13
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2825 predictions. Top by Δscore:

Variant	Effect	Δscore
1:207652721:A:G	donor_gain	1.0000
1:207678296:GG:G	donor_gain	1.0000
1:207678297:GG:G	donor_gain	1.0000
1:207683954:GACA:G	donor_gain	1.0000
1:207683958:G:GG	donor_gain	1.0000
1:207697501:A:AG	acceptor_gain	1.0000
1:207697501:AGTAT:A	acceptor_gain	1.0000
1:207697502:G:GC	acceptor_gain	1.0000
1:207697502:GT:G	acceptor_gain	1.0000
1:207697502:GTA:G	acceptor_gain	1.0000
1:207697502:GTAT:G	acceptor_gain	1.0000
1:207697502:GTATG:G	acceptor_gain	1.0000
1:207697617:GATC:G	donor_gain	1.0000
1:207697675:TGAAG:T	donor_loss	1.0000
1:207697676:GAAGG:G	donor_loss	1.0000
1:207697681:T:A	donor_loss	1.0000
1:207697765:TTCCA:T	acceptor_loss	1.0000
1:207697766:TCCA:T	acceptor_loss	1.0000
1:207697767:CCAG:C	acceptor_loss	1.0000
1:207697768:CAGT:C	acceptor_loss	1.0000
1:207697769:A:AG	acceptor_gain	1.0000
1:207697769:A:AT	acceptor_loss	1.0000
1:207697769:AGT:A	acceptor_gain	1.0000
1:207697770:G:GG	acceptor_gain	1.0000
1:207697770:GT:G	acceptor_gain	1.0000
1:207697770:GTG:G	acceptor_gain	1.0000
1:207697770:GTGA:G	acceptor_gain	1.0000
1:207697770:GTGAA:G	acceptor_gain	1.0000
1:207697869:GAAGG:G	donor_gain	1.0000
1:207697871:AGG:A	donor_gain	1.0000

AlphaMissense

3746 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:207694723:G:C	W278C	0.997
1:207694723:G:T	W278C	0.997
1:207677543:G:C	W84C	0.992
1:207677543:G:T	W84C	0.992
1:207683932:G:C	W146C	0.992
1:207683932:G:T	W146C	0.992
1:207694540:G:C	W217C	0.992
1:207694540:G:T	W217C	0.992
1:207694721:T:A	W278R	0.988
1:207694721:T:C	W278R	0.988
1:207697654:G:C	W338C	0.984
1:207697654:G:T	W338C	0.984
1:207699249:G:C	W401C	0.984
1:207699249:G:T	W401C	0.984
1:207694538:T:A	W217R	0.979
1:207694538:T:C	W217R	0.979
1:207694703:T:A	C272S	0.979
1:207694704:G:C	C272S	0.979
1:207677562:T:A	C91S	0.976
1:207677563:G:C	C91S	0.976
1:207677484:T:A	C65S	0.975
1:207677485:G:C	C65S	0.975
1:207694508:T:A	C207S	0.974
1:207694509:G:C	C207S	0.974
1:207694559:T:A	C224S	0.973
1:207694560:G:C	C224S	0.973
1:207677541:T:A	W84R	0.972
1:207677541:T:C	W84R	0.972
1:207683930:T:A	W146R	0.968
1:207683930:T:C	W146R	0.968

dbSNP variants (sampled 300 via entrez): RS1000018085 (1:207681988 G>A), RS1000020108 (1:207720710 A>C,G), RS1000126229 (1:207643224 A>G), RS1000215624 (1:207669622 G>A,T), RS1000286858 (1:207653915 T>G), RS1000294141 (1:207714659 G>A,C), RS1000343560 (1:207653515 C>G,T), RS1000397680 (1:207700265 CTTATA>C), RS1000432161 (1:207699996 A>G), RS1000505090 (1:207699796 T>C), RS1000551371 (1:207659753 G>A), RS1000661140 (1:207705534 A>G), RS1000705555 (1:207664842 A>G), RS1000762659 (1:207710810 G>A,T), RS1000798928 (1:207648598 T>C)

Disease associations

OMIM: gene MIM:605886 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST000283_6	LDL cholesterol	2.000000e-07
GCST001120_5	Erythrocyte sedimentation rate	2.000000e-09
GCST002539_34	Schizophrenia	4.000000e-08
GCST006803_51	Schizophrenia	3.000000e-07
GCST007095_101	Systolic blood pressure	3.000000e-08
GCST007095_102	Systolic blood pressure	3.000000e-07
GCST007096_118	Pulse pressure	2.000000e-09
GCST007097_78	Pulse pressure	6.000000e-08
GCST007097_79	Pulse pressure	3.000000e-07
GCST007099_162	Systolic blood pressure	2.000000e-07
GCST007742_16	Iris heterochromicity	4.000000e-06
GCST007742_6	Iris heterochromicity	4.000000e-06
GCST009597_172	Multiple sclerosis	1.000000e-07
GCST010002_375	Refractive error	2.000000e-54

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0009764	eye colour measurement

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
rs7527798	CR1L		0.00	0

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	8
trichostatin A	affects cotreatment, increases expression	3
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
alpha phellandrene	decreases expression	1
bisphenol A	decreases methylation	1
sulforaphane	increases expression	1
perfluorooctanoic acid	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Benzo(a)pyrene	affects methylation	1
Lipopolysaccharides	increases expression, decreases reaction	1
Phthalic Acids	increases methylation	1
Rotenone	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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