CREB3L2

Summary

CREB3L2 (cAMP responsive element binding protein 3 like 2, HGNC:23720) is a protein-coding gene on chromosome 7q33, encoding Cyclic AMP-responsive element-binding protein 3-like protein 2 (Q70SY1). Transcription factor involved in unfolded protein response (UPR).

This gene encodes a member of the oasis bZIP transcription factor family. Members of this family can dimerize but form homodimers only. The encoded protein is a transcriptional activator. Translocations between this gene on chromosome 7 and the gene fused in sarcoma on chromosome 16 can be found in some tumors. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 64764 — RefSeq curated summary.

At a glance

• GWAS associations: 23
• Clinical variants (ClinVar): 86 total — 1 pathogenic
• MANE Select transcript: NM_194071

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23720
Approved symbol	CREB3L2
Name	cAMP responsive element binding protein 3 like 2
Location	7q33
Locus type	gene with protein product
Status	Approved
Aliases	BBF2H7, TCAG_1951439
Ensembl gene	ENSG00000182158
Ensembl biotype	protein_coding
OMIM	608834
Entrez	64764

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000330387, ENST00000420629, ENST00000452463, ENST00000456390, ENST00000458726, ENST00000468127, ENST00000898368

RefSeq mRNA: 3 — MANE Select: NM_194071 NM_001253775, NM_001318246, NM_194071

CCDS: CCDS34760, CCDS59083

Canonical transcript exons

ENST00000330387 — 12 exons

Exon	Start	End
ENSE00001295416	137874979	137880551
ENSE00001334633	137915837	137916012
ENSE00001839636	138001604	138002086
ENSE00002431469	137908252	137908436
ENSE00002434476	137882412	137882628
ENSE00002448026	137901354	137901422
ENSE00002480199	137884995	137885121
ENSE00002484699	137885403	137885502
ENSE00002504571	137905702	137905848
ENSE00002509347	137903959	137904017
ENSE00002525295	137912991	137913078
ENSE00003539834	137928150	137928366

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 97.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.0578 / max 1257.5720, expressed in 1827 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86440	25.8877	1775
86441	10.2696	1770
86435	2.4168	472
86434	2.1538	414
86423	2.1207	1072
86439	1.3442	676
86424	0.9802	627
86438	0.6640	405
86421	0.5241	221
86422	0.4959	256

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
saphenous vein	UBERON:0007318	97.75	gold quality
tibia	UBERON:0000979	97.68	gold quality
synovial joint	UBERON:0002217	97.42	gold quality
pylorus	UBERON:0001166	97.33	gold quality
cauda epididymis	UBERON:0004360	97.15	gold quality
urethra	UBERON:0000057	97.09	gold quality
superficial temporal artery	UBERON:0001614	96.96	gold quality
corpus epididymis	UBERON:0004359	96.93	gold quality
cardia of stomach	UBERON:0001162	96.77	gold quality
trachea	UBERON:0003126	96.77	gold quality
caput epididymis	UBERON:0004358	96.62	gold quality
trigeminal ganglion	UBERON:0001675	96.60	gold quality
stromal cell of endometrium	CL:0002255	96.54	gold quality
jejunal mucosa	UBERON:0000399	96.44	gold quality
placenta	UBERON:0001987	96.38	gold quality
cartilage tissue	UBERON:0002418	96.14	gold quality
dorsal root ganglion	UBERON:0000044	96.06	gold quality
pericardium	UBERON:0002407	96.04	gold quality
renal medulla	UBERON:0000362	95.98	gold quality
palpebral conjunctiva	UBERON:0001812	95.84	gold quality
choroid plexus epithelium	UBERON:0003911	95.74	gold quality
decidua	UBERON:0002450	95.37	gold quality
mammary duct	UBERON:0001765	95.35	gold quality
secondary oocyte	CL:0000655	95.22	gold quality
vena cava	UBERON:0004087	95.22	gold quality
parotid gland	UBERON:0001831	94.80	gold quality
epithelium of mammary gland	UBERON:0003244	94.79	gold quality
blood vessel layer	UBERON:0004797	94.74	gold quality
trabecular bone tissue	UBERON:0002483	94.72	gold quality
colonic epithelium	UBERON:0000397	94.54	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-CURD-88	yes	82.71
E-CURD-46	yes	45.13
E-CURD-119	yes	40.91
E-ANND-3	yes	30.87
E-MTAB-8410	yes	27.72
E-MTAB-9543	yes	19.49
E-MTAB-9067	yes	13.31
E-HCAD-35	yes	8.59
E-MTAB-10553	yes	8.33

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
BDNF
CD74
SEC24C

miRNA regulators (miRDB)

268 targeting CREB3L2, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821

Literature-anchored findings (GeneRIF, showing 19)

• BBF2H7 was fused with FUS in a low grade myxoid liposarcoma. (PMID:12915480)
• CREB3L2 is not only structurally, but also functionally very similar to CREB3L1. (PMID:17117415)
• BBF2H7, a novel transmembrane bZIP transcription factor, is a new type of endoplasmic reticulumm stress transducer. (PMID:17178827)
• Presence of FUS/CREB3L2 and FUS/CREB3L1 in low-grade fibromyxoid sarcoma and sclerosing epithelioid fibrosarcoma suggests these neoplasms may be related. (PMID:17721195)
• findings identify a novel CREB3L2-PPARgamma gene fusion mutation in thyroid carcinoma and reveal a thyroid signaling pathway that is regulated by intramembrane proteolysis and disrupted in cancer (PMID:18757431)
• We characterized the promoter region of CREB3L2, showing that it is asymmetrically bidirectional (PMID:19212619)
• Fusion of the FUS and CREB3L2 genes in a supernumerary ring chromosome is associated with low-grade fibromyxoid sarcoma. (PMID:20471519)
• We characterized a widely expressed transcript of CREB3L2 generated by an intronic polyadenylation site in intron 4 of the gene. (PMID:20878102)
• The human Creb3L2 can activate SPCG transcription in a heterologous system(Drosophila embryos), which suggests a general and direct role for this family of bZip transcription factors in mediating high-level secretory capacity. (PMID:21041443)
• FUS-CREB3L2/L1-positive sarcomas show a specific gene expression profile with upregulation of CD24 and FOXL1. (PMID:21536545)
• the BBF2H7-mediated Sec23A pathway is required for ER-to-Golgi procollagen trafficking to promote collagen synthesis (PMID:22495181)
• Fbxw7 controls osteogenesis and chondrogenesis by targeting OASIS and BBF2H7, respectively, for degradation. (PMID:23955342)
• These data suggest that the secreted luminal BBF2H7 C-terminus is involved in Hedgehog ligand-dependent cancer cell proliferation through activation of Hedgehog signaling. BBF2H7 C-terminus may be a novel target for the development of anticancer drugs. (PMID:25955804)
• UPR transducer BBF2H7 allows export of type II collagen in a cargo- and developmental stage-specific manner. (PMID:28500182)
• Transduction with BBF2H7/CREB3L2 upregulates SEC23A protein in erythroblasts and partially corrects the hypo-glycosylation phenotype associated with CDAII. (PMID:29536501)
• found BBF2H7-derived small peptide fragments located between the site-1 protease and site-1 protease cleavage sites in cells exposed to ER stress (PMID:31914686)
• MicroRNA-92b-3p promotes the progression of liver fibrosis by targeting CREB3L2 through the JAK/STAT signaling pathway. (PMID:33618248)
• Comparative Analysis of CREB3 and CREB3L2 Protein Expression in HEK293 Cells. (PMID:33803345)
• Single-cell analysis reveals androgen receptor regulates the ER-to-Golgi trafficking pathway with CREB3L2 to drive prostate cancer progression. (PMID:34611310)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	creb3l2	ENSDARG00000063563
mus_musculus	Creb3l2	ENSMUSG00000038648
drosophila_melanogaster	CrebA	FBGN0004396
drosophila_melanogaster	Atf6	FBGN0033010
drosophila_melanogaster	CrebB	FBGN0265784
caenorhabditis_elegans		WBGENE00000222
caenorhabditis_elegans		WBGENE00000793
caenorhabditis_elegans		WBGENE00016162

Paralogs (9): CREB3L3 (ENSG00000060566), CREM (ENSG00000095794), CREB3 (ENSG00000107175), ATF6 (ENSG00000118217), CREB1 (ENSG00000118260), ATF1 (ENSG00000123268), CREB3L4 (ENSG00000143578), CREB3L1 (ENSG00000157613), ATF6B (ENSG00000213676)

Protein

Protein identifiers

Cyclic AMP-responsive element-binding protein 3-like protein 2 — Q70SY1 (reviewed: Q70SY1)

Alternative names: BBF2 human homolog on chromosome 7

All UniProt accessions (3): Q70SY1, C9JPH0, H7C1W8

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor involved in unfolded protein response (UPR). In the absence of endoplasmic reticulum (ER) stress, inserted into ER membranes, with N-terminal DNA-binding and transcription activation domains oriented toward the cytosolic face of the membrane. In response to ER stress, transported to the Golgi, where it is cleaved in a site-specific manner by resident proteases S1P/MBTPS1 and S2P/MBTPS2. The released N-terminal cytosolic domain is translocated to the nucleus to effect transcription of specific target genes. Plays a critical role in chondrogenesis by activating the transcription of SEC23A, which promotes the transport and secretion of cartilage matrix proteins, and possibly that of ER biogenesis-related genes. In a neuroblastoma cell line, protects cells from ER stress-induced death. In vitro activates transcription of target genes via direct binding to the CRE site.

Subunit / interactions. Binds DNA as a dimer.

Subcellular location. Endoplasmic reticulum membrane Nucleus.

Tissue specificity. Widely expressed with highest levels in placenta, lung, spleen and intestine, and lowest levels in heart, brain, skeletal muscle, thymus, colon and leukocytes. In fetal tissues, the weakest expression is detected in brain and heart.

Post-translational modifications. Upon ER stress, translocated to the Golgi apparatus, where it is processed by regulated intramembrane proteolysis (RIP) to release the cytosol-facing N-terminal transcription factor domain. The cleavage is performed sequentially by site-1 and site-2 proteases (S1P/MBTPS1 and S2P/MBTPS2). N-glycosylated. Ubiquitinated by HRD1/SYVN1; undergoes ‘Lys-48’-linked ubiquitination, followed by rapid proteasomal degradation under normal conditions. Upon ER stress, SYVN1 E3 ubiquitin-protein ligase dissociates from its substrate, ubiquitination does not occur and CREB3L2 is stabilized.

Disease relevance. A chromosomal aberration involving CREB3L2 is found in low grade fibromyxoid sarcoma (LGFMS). Translocation t(7;16)(q33;p11) with FUS.

Induction. Up-regulated by ER stress at the transcript and protein levels, the increase at the protein level is much higher than at the transcript level. This induction is accompanied by increased proteolytic cleavage that releases the N-terminal transcription factor domain.

Similarity. Belongs to the bZIP family. ATF subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q70SY1-1	1	yes
Q70SY1-2	2
Q70SY1-3	3

RefSeq proteins (3): NP_001240704, NP_001305175, NP_919047* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004827	bZIP	Domain
IPR046347	bZIP_sf	Homologous_superfamily

Pfam: PF00170

UniProt features (23 total): glycosylation site 3, splice variant 3, region of interest 3, chain 2, compositionally biased region 2, modified residue 2, topological domain 2, sequence variant 2, cross-link 1, transmembrane region 1, domain 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q70SY1-F1	55.95	0.14

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): 93, 191, 178

Glycosylation sites (3): 480, 504, 517

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8874211	CREB3 factors activate genes

MSigDB gene sets: 351 (showing top): RNGTGGGC_UNKNOWN, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, LFA1_Q6, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOZGIT_ESR1_TARGETS_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, COUP_01, PATIL_LIVER_CANCER, GOBP_ENDOPLASMIC_RETICULUM_TO_GOLGI_VESICLE_MEDIATED_TRANSPORT, ATF1_Q6, GOBP_CHONDROCYTE_DIFFERENTIATION, KEGG_PROSTATE_CANCER

GO Biological Process (9): chondrocyte differentiation (GO:0002062), regulation of transcription by RNA polymerase II (GO:0006357), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), response to unfolded protein (GO:0006986), response to endoplasmic reticulum stress (GO:0034976), positive regulation of DNA-templated transcription (GO:0045893), cartilage development (GO:0051216), regulation of DNA-templated transcription (GO:0006355), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (7): transcription cis-regulatory region binding (GO:0000976), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), cAMP response element binding (GO:0035497), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Unfolded Protein Response (UPR)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
transcription by RNA polymerase II	2
cytoplasm	2
DNA-templated transcription	2
regulation of transcription by RNA polymerase II	2
intracellular membrane-bounded organelle	2
cell differentiation	1
cartilage development	1
intercellular transport	1
intracellular transport	1
Golgi vesicle transport	1
response to topologically incorrect protein	1
cellular response to stress	1
positive regulation of RNA biosynthetic process	1
skeletal system development	1
animal organ development	1
connective tissue development	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
RNA polymerase II cis-regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
chromosome	1
nuclear lumen	1
endomembrane system	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1

Protein interactions and networks

STRING

720 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CREB3L2	FUS	P35637	888
CREB3L2	ATF5	Q9Y2D1	806
CREB3L2	A0A087WTZ4	A0A087WTZ4	648
CREB3L2	ATF1	P18846	645
CREB3L2	MBTPS1	Q14703	622
CREB3L2	MBTPS2	O43462	621
CREB3L2	FRS2	Q8WU20	615
CREB3L2	MUC4	Q99102	573
CREB3L2	SEC23A	Q15436	553
CREB3L2	MCL1	Q07820	541
CREB3L2	SEC24D	O94855	538
CREB3L2	FABP7	O15540	513
CREB3L2	SLC7A11	Q9UPY5	510
CREB3L2	EWSR1	Q01844	480
CREB3L2	XBP1	P17861	463

IntAct

21 interactions, top by confidence:

A	B	Type	Score
CREB3L1	AP3B1	psi-mi:“MI:0914”(association)	0.530
CREB3	MYO9A	psi-mi:“MI:0914”(association)	0.530
Dynll1		psi-mi:“MI:0915”(physical association)	0.400
PCNA	CREB3L2	psi-mi:“MI:0915”(physical association)	0.370
PXN	CREB3L2	psi-mi:“MI:0915”(physical association)	0.370
RGS16	CREB3L2	psi-mi:“MI:0915”(physical association)	0.370
CREB3L2	GCFC2	psi-mi:“MI:0915”(physical association)	0.370
CREB3L2	GAS7	psi-mi:“MI:0915”(physical association)	0.370
CREB3L2	GULP1	psi-mi:“MI:0915”(physical association)	0.370
CEP19	CREB3L2	psi-mi:“MI:0915”(physical association)	0.370
CREB3	OGT	psi-mi:“MI:0914”(association)	0.350
CREB3L3	AP3B1	psi-mi:“MI:0914”(association)	0.350
CREB3L2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
SLC27A6	NBAS	psi-mi:“MI:0914”(association)	0.350
PTP4A1	CREB3L2	psi-mi:“MI:0915”(physical association)	0.000
CREB3L2	RND1	psi-mi:“MI:0915”(physical association)	0.000
ZNF212	CREB3L2	psi-mi:“MI:0915”(physical association)	0.000
CREB3L2		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (29): CREB3L2 (Affinity Capture-MS), CREB3L2 (Affinity Capture-MS), CREB3L2 (Affinity Capture-MS), CREB3L2 (Affinity Capture-MS), CREB3L2 (Affinity Capture-MS), CREB3L2 (Affinity Capture-RNA), CREB3L2 (Affinity Capture-RNA), CREB3L2 (Affinity Capture-MS), CREB3L2 (Two-hybrid), CREB3L2 (Affinity Capture-MS), CREB3L2 (Affinity Capture-MS), CREB3L2 (Affinity Capture-MS), CREB3L2 (Proximity Label-MS), CREB3L2 (Proximity Label-MS), CREB3L2 (Proximity Label-MS)

ESM2 similar proteins: A1L224, A2VD01, D3ZLB7, F6VAN0, G3V909, O02761, O35451, O43889, O77628, O88479, O94983, O97930, P01100, P01101, P01102, P0C0N8, P0C0N9, P11939, P12841, P18850, P20389, P38532, Q00613, Q08CW8, Q08DJ8, Q1LYG4, Q3SYZ3, Q502F0, Q56TN0, Q56TT7, Q5FVM5, Q5RCM9, Q5UEM7, Q5UEM8, Q61817, Q64210, Q66HA2, Q68CJ9, Q6QDP7, Q6ZPJ0

Diamond homologs: A1L224, A2VD01, O43889, O44743, P29747, Q08CW8, Q1LYG4, Q3SYZ3, Q4JFH9, Q502F0, Q5FVM5, Q5RCM9, Q5UEM7, Q5UEM8, Q61817, Q66HA2, Q68CJ9, Q6QDP7, Q70SY1, Q8BH52, Q8SQ19, Q8TEY5, Q91XE9, Q96BA8, Q9D2A5, Q9Z125, F6VAN0, G3V909, O35451, P18850, Q99941, Q54Y73, O22208, O24646, P14233, Q54WN7, Q554P0, Q55E93, Q6AU90, Q8LIB3

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
MBTPS1	up-regulates	CREB3L2	cleavage
Unfolded_Proteins	up-regulates	CREB3L2

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	66
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3062984	GRCh37/hg19 7q33-36.3(chr7:137456457-159119707)x3	Pathogenic

SpliceAI

2615 predictions. Top by Δscore:

Variant	Effect	Δscore
7:137884991:TTA:T	donor_loss	1.0000
7:137884993:A:AC	donor_gain	1.0000
7:137884993:A:AT	donor_loss	1.0000
7:137884993:AC:A	donor_gain	1.0000
7:137884994:C:A	donor_loss	1.0000
7:137884994:C:CC	donor_gain	1.0000
7:137884994:CC:C	donor_gain	1.0000
7:137884994:CCCA:C	donor_gain	1.0000
7:137885118:CAAC:C	acceptor_gain	1.0000
7:137901348:ACTTA:A	donor_loss	1.0000
7:137901349:CTTAC:C	donor_loss	1.0000
7:137901351:TACCT:T	donor_loss	1.0000
7:137901352:A:T	donor_loss	1.0000
7:137901418:CCACT:C	acceptor_gain	1.0000
7:137901419:CACT:C	acceptor_gain	1.0000
7:137901419:CACTC:C	acceptor_gain	1.0000
7:137901420:ACT:A	acceptor_gain	1.0000
7:137901421:CT:C	acceptor_gain	1.0000
7:137901421:CTC:C	acceptor_gain	1.0000
7:137901422:TC:T	acceptor_loss	1.0000
7:137901422:TCT:T	acceptor_gain	1.0000
7:137901423:C:A	acceptor_gain	1.0000
7:137901423:C:CC	acceptor_gain	1.0000
7:137901424:T:A	acceptor_loss	1.0000
7:137901426:C:CT	acceptor_gain	1.0000
7:137901427:A:T	acceptor_gain	1.0000
7:137903957:A:AC	donor_gain	1.0000
7:137903958:C:CA	donor_gain	1.0000
7:137904015:AATC:A	acceptor_loss	1.0000
7:137904016:ATC:A	acceptor_loss	1.0000

AlphaMissense

3365 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:137885109:A:G	C386R	1.000
7:137885476:A:G	L357P	1.000
7:137885485:A:G	L354P	1.000
7:137885497:A:G	L350P	1.000
7:137901369:A:G	L343P	1.000
7:137901390:A:G	L336P	1.000
7:137903968:A:G	L322P	1.000
7:137903985:T:A	K316N	1.000
7:137903985:T:G	K316N	1.000
7:137903988:C:A	K315N	1.000
7:137903988:C:G	K315N	1.000
7:137903990:T:C	K315E	1.000
7:137903991:C:A	K314N	1.000
7:137903991:C:G	K314N	1.000
7:137903993:T:C	K314E	1.000
7:137903994:T:A	R313S	1.000
7:137903994:T:G	R313S	1.000
7:137903995:C:G	R313T	1.000
7:137903997:C:A	R312S	1.000
7:137903997:C:G	R312S	1.000
7:137903998:C:A	R312M	1.000
7:137903998:C:G	R312T	1.000
7:137903999:T:C	R312G	1.000
7:137904000:A:C	S311R	1.000
7:137904000:A:T	S311R	1.000
7:137904002:T:G	S311R	1.000
7:137904006:C:A	Q309H	1.000
7:137904006:C:G	Q309H	1.000
7:137904007:T:G	Q309P	1.000
7:137904010:G:A	A308V	1.000

dbSNP variants (sampled 300 via entrez): RS1000020412 (7:137886989 C>T), RS1000103674 (7:137884680 C>G), RS1000125685 (7:137929970 T>C), RS1000129177 (7:137994761 A>C,G), RS1000229217 (7:138001395 G>C), RS1000245226 (7:137892845 G>C), RS1000251944 (7:137910861 C>T), RS1000253035 (7:137954013 T>C), RS1000260630 (7:137967940 G>A), RS1000271005 (7:137960950 A>G), RS1000282555 (7:137890595 T>C), RS1000337998 (7:137941184 G>C), RS1000394594 (7:137947869 C>G,T), RS1000401431 (7:137955422 T>C), RS1000408407 (7:137914243 A>C,T)

Disease associations

OMIM: gene MIM:608834 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST007096_116	Pulse pressure	3.000000e-08
GCST007294_18	Body fat distribution (trunk fat ratio)	2.000000e-07
GCST007294_37	Body fat distribution (trunk fat ratio)	1.000000e-06
GCST008045_13	Total cholesterol levels	2.000000e-08
GCST008045_35	Total cholesterol levels	2.000000e-06
GCST008077_34	LDL cholesterol levels	2.000000e-06
GCST008077_78	LDL cholesterol levels	9.000000e-08
GCST008078_121	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2.000000e-09
GCST008078_77	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	3.000000e-07
GCST008079_155	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	8.000000e-15
GCST008079_79	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	3.000000e-10
GCST008086_77	LDL cholesterol levels in current drinkers	8.000000e-08
GCST008086_90	LDL cholesterol levels in current drinkers	6.000000e-07
GCST008839_133	Height	4.000000e-11
GCST009391_1066	Metabolite levels	5.000000e-06
GCST010002_265	Refractive error	2.000000e-09
GCST012226_656	Waist circumference adjusted for body mass index	8.000000e-10
GCST012227_138	Hip circumference adjusted for BMI	6.000000e-09
GCST90002393_71	Monocyte count	1.000000e-10
GCST90013406_235	Liver enzyme levels (alkaline phosphatase)	2.000000e-12
GCST90020024_124	A body shape index	3.000000e-08
GCST90020029_898	Waist circumference adjusted for body mass index	2.000000e-12
GCST90020029_900	Waist circumference adjusted for body mass index	1.000000e-08

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0004341	body fat distribution
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0010364	lysophosphatidylcholine 20:5 measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0005091	monocyte count
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	5
trichostatin A	affects cotreatment, increases expression	3
Benzo(a)pyrene	decreases expression, decreases methylation	3
sodium arsenite	increases expression	2
Tobacco Smoke Pollution	increases expression	2
Tunicamycin	increases expression	2
Cyclosporine	decreases expression, increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
Thapsigargin	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	increases methylation	1
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
geraniol	increases expression	1
lead acetate	increases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
cobaltous chloride	decreases expression	1
1-aminomethylphosphonic acid	increases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
diallyl trisulfide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Glyphosate	decreases expression	1
Atrazine	increases expression	1
Cadmium	decreases expression, increases abundance	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B0W9	NCC-LGFMS1-C1	Cancer cell line	Female
CVCL_B1P7	Abcam HeLa CREB3L2 KO	Cancer cell line	Female
CVCL_E0AW	Ubigene HeLa CREB3L2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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