CDC37L1

Summary

CDC37L1 (cell division cycle 37 like 1, HSP90 cochaperone, HGNC:17179) is a protein-coding gene on chromosome 9p24.1, encoding Hsp90 co-chaperone Cdc37-like 1 (Q7L3B6). Co-chaperone that binds to numerous proteins and promotes their interaction with Hsp70 and Hsp90.

CDC37L1 is a cytoplasmic phosphoprotein that exists in complex with HSP90 (HSPCA; MIM 140571) as well as several other proteins involved in HSP90-mediated protein folding (Scholz et al., 2001 [PubMed 11413142]).

Source: NCBI Gene 55664 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 61 total — 2 pathogenic
• MANE Select transcript: NM_017913

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17179
Approved symbol	CDC37L1
Name	cell division cycle 37 like 1, HSP90 cochaperone
Location	9p24.1
Locus type	gene with protein product
Status	Approved
Aliases	HARC, FLJ20639, CDC37B
Ensembl gene	ENSG00000106993
Ensembl biotype	protein_coding
OMIM	610346
Entrez	55664

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000381854, ENST00000381858, ENST00000479095, ENST00000906222, ENST00000906223, ENST00000906224, ENST00000906225

RefSeq mRNA: 1 — MANE Select: NM_017913 NM_017913

CCDS: CCDS6454

Canonical transcript exons

ENST00000381854 — 7 exons

Exon	Start	End
ENSE00000687745	4684877	4685158
ENSE00000687749	4688513	4688606
ENSE00000687751	4697096	4697211
ENSE00000687754	4697757	4697879
ENSE00000687759	4701864	4702028
ENSE00001490055	4706011	4708399
ENSE00001816542	4679569	4679899

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 94.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.3431 / max 325.4795, expressed in 1801 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
95905	15.2432	1789
95906	2.0760	1167
95908	1.7965	923
95907	1.2274	775

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	94.92	gold quality
muscle of leg	UBERON:0001383	94.43	gold quality
tibialis anterior	UBERON:0001385	93.40	gold quality
muscle organ	UBERON:0001630	92.41	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.15	gold quality
heart right ventricle	UBERON:0002080	91.50	gold quality
cartilage tissue	UBERON:0002418	91.38	gold quality
mucosa of stomach	UBERON:0001199	91.03	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.65	gold quality
calcaneal tendon	UBERON:0003701	90.17	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.00	gold quality
deltoid	UBERON:0001476	89.94	silver quality
right atrium auricular region	UBERON:0006631	89.86	gold quality
oocyte	CL:0000023	89.70	gold quality
heart left ventricle	UBERON:0002084	89.70	gold quality
right lobe of liver	UBERON:0001114	89.65	gold quality
cardiac ventricle	UBERON:0002082	89.55	gold quality
skeletal muscle tissue	UBERON:0001134	89.38	gold quality
secondary oocyte	CL:0000655	89.18	gold quality
liver	UBERON:0002107	89.12	gold quality
heart	UBERON:0000948	89.09	gold quality
buccal mucosa cell	CL:0002336	89.07	gold quality
cardiac atrium	UBERON:0002081	89.04	gold quality
gluteal muscle	UBERON:0002000	88.87	gold quality
popliteal artery	UBERON:0002250	88.62	gold quality
tibial artery	UBERON:0007610	88.62	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.48	gold quality
biceps brachii	UBERON:0001507	88.45	gold quality
lower esophagus	UBERON:0013473	88.42	gold quality
adrenal tissue	UBERON:0018303	88.26	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.61

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

176 targeting CDC37L1, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-551B-5P	99.96	71.28	3493

Literature-anchored findings (GeneRIF, showing 2)

• Harc forms dimers in vitro. The structural similarities between Harc and Cdc37 suggest that Harc may function to regulate the Hsp90-mediated folding of Cdc37-dependent protein kinases into functional conformations via dimerization with Cdc37. (PMID:15850399)
• C-terminal domain of Harc is a key determinant of its cochaperone functions (PMID:18052042)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdc37l1	ENSDARG00000044265
mus_musculus	Cdc37l1	ENSMUSG00000024780
rattus_norvegicus	Cdc37l1	ENSRNOG00000010967
drosophila_melanogaster	Cdc37	FBGN0011573
caenorhabditis_elegans		WBGENE00019497
caenorhabditis_elegans		WBGENE00021097

Paralogs (1): CDC37 (ENSG00000105401)

Protein

Protein identifiers

Hsp90 co-chaperone Cdc37-like 1 — Q7L3B6 (reviewed: Q7L3B6)

Alternative names: Hsp90-associating relative of Cdc37

All UniProt accessions (2): Q7L3B6, B1AL69

UniProt curated annotations — full annotation on UniProt →

Function. Co-chaperone that binds to numerous proteins and promotes their interaction with Hsp70 and Hsp90.

Subunit / interactions. Self-associates. Forms complexes with Hsp70 and Hsp90. Interacts with CDC37, FKBP4, PPID and STIP1.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in brain, heart, kidney, liver, placenta and skeletal muscle.

Similarity. Belongs to the CDC37 family.

RefSeq proteins (1): NP_060383* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004918	Cdc37	Family
IPR013874	Cdc37_Hsp90-bd	Domain
IPR038189	Cdc37_Hsp90-bd_sf	Homologous_superfamily

Pfam: PF08565

UniProt features (14 total): region of interest 5, sequence conflict 3, modified residue 2, chain 1, sequence variant 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7L3B6-F1	72.63	0.43

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 (2): 32, 88

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-109582	Hemostasis
R-HSA-76002	Platelet activation, signaling and aggregation
R-HSA-76005	Response to elevated platelet cytosolic Ca2+

MSigDB gene sets: 184 (showing top): AAGCAAT_MIR137, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, TGCACTT_MIR519C_MIR519B_MIR519A, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, RACCACAR_AML_Q6, CHEN_LVAD_SUPPORT_OF_FAILING_HEART_UP, GOBP_PROTEIN_MATURATION, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, WANG_LMO4_TARGETS_DN, GOBP_PROTEIN_STABILIZATION, CAIRO_HEPATOBLASTOMA_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_AND_CANCER_BOX4_DN

GO Biological Process (2): protein folding (GO:0006457), protein stabilization (GO:0050821)

GO Molecular Function (4): heat shock protein binding (GO:0031072), obsolete unfolded protein binding (GO:0051082), protein-folding chaperone binding (GO:0051087), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), cytoplasm (GO:0005737), cytosol (GO:0005829), platelet dense granule lumen (GO:0031089)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1
Hemostasis	1
Platelet activation, signaling and aggregation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein binding	2
cellular process	1
protein maturation	1
regulation of protein stability	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
secretory granule lumen	1
platelet dense granule	1

Protein interactions and networks

STRING

1151 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDC37L1	PTGES3	Q15185	819
CDC37L1	STIP1	P31948	781
CDC37L1	HSP90AA1	P07900	747
CDC37L1	HCK	P08631	678
CDC37L1	HSPA4	P34932	665
CDC37L1	PPID	Q08752	632
CDC37L1	FKBP4	Q02790	594
CDC37L1	HSP90AB1	P08238	581
CDC37L1	SPP2	Q13103	552
CDC37L1	AHSA1	O95433	532
CDC37L1	HSPA1A	P08107	524
CDC37L1	RAF1	P04049	448
CDC37L1	ECHDC2	Q86YB7	407
CDC37L1	HSF2BP	O75031	402
CDC37L1	TRAPPC14	Q8WVR3	393

IntAct

30 interactions, top by confidence:

A	B	Type	Score
HSP90AB1	CDC37L1	psi-mi:“MI:0915”(physical association)	0.850
CDC37L1	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.850
HSP90AB1	HSP90AA1	psi-mi:“MI:0914”(association)	0.840
HSP90AA1	CHUK	psi-mi:“MI:0914”(association)	0.670
HSP90AB1	CHUK	psi-mi:“MI:0914”(association)	0.670
BRK1	CDC37L1	psi-mi:“MI:0915”(physical association)	0.560
CDC37L1	HSP90AA1	psi-mi:“MI:0915”(physical association)	0.560
FKBP6	EEF2K	psi-mi:“MI:0914”(association)	0.530
STK35	HSP90AA1	psi-mi:“MI:0914”(association)	0.530
STIP1	CDC37L1	psi-mi:“MI:0915”(physical association)	0.500
USP19	CDC37L1	psi-mi:“MI:0915”(physical association)	0.400
CDC37L1	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
SPATA24	CDC37L1	psi-mi:“MI:0915”(physical association)	0.400
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
STK35	HSP90AA1	psi-mi:“MI:0914”(association)	0.350
FKBP6	VGF	psi-mi:“MI:0914”(association)	0.350
HSP90AB1	MGST3	psi-mi:“MI:0914”(association)	0.350
CDC37L1	EL52	psi-mi:“MI:0914”(association)	0.350
FKBP5	EL52	psi-mi:“MI:0914”(association)	0.350
CDC37L1	tcaA1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (66): CDC37L1 (Two-hybrid), CDC37L1 (Affinity Capture-MS), CDC37L1 (Synthetic Growth Defect), CDC37L1 (Affinity Capture-MS), CDC37L1 (Affinity Capture-MS), HSP90AA1 (Affinity Capture-Western), CDC37L1 (Affinity Capture-Western), STIP1 (Affinity Capture-Western), HSPA1A (Affinity Capture-Western), CDC37L1 (Affinity Capture-Western), CDC37L1 (Affinity Capture-MS), CDC37L1 (Affinity Capture-MS), CDC37L1 (Affinity Capture-RNA), CDC37L1 (Affinity Capture-MS), CDC37L1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0D9SF12, A2A8T7, A6H7E2, A6NF36, A6NFA0, A6NI87, E1C7U0, P03246, P03247, P0DO92, P14355, P14683, Q0VG49, Q1HVF6, Q32LN6, Q3KPU7, Q3KSS3, Q4V7D2, Q4ZG55, Q5DU28, Q5JX69, Q5JX71, Q5R7E2, Q5U4U4, Q642A3, Q6NRW0, Q6P1U0, Q6P4J6, Q6P9N1, Q6PEX7, Q6X4T0, Q7L3B6, Q7SYV9, Q7T346, Q80Y73, Q8BJS8, Q8CF25, Q8IWB6, Q8N6T0, Q8NCU1

Diamond homologs: A6H754, A7YY97, O57476, Q16543, Q24276, Q24740, Q28HY7, Q5EAC6, Q5RA87, Q5XIC3, Q61081, Q63692, Q7L3B6, Q9CZP7, Q9DGQ7, O02108, O94740, P06101, Q8X1E6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	44
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
3896738	NC_000009.11:g.(?134929)(8733886_?)del	Pathogenic
563670	GRCh37/hg19 9p24.3-24.1(chr9:203861-4959039)x1	Pathogenic

SpliceAI

999 predictions. Top by Δscore:

Variant	Effect	Δscore
9:4684876:GAT:G	acceptor_gain	1.0000
9:4685144:G:GT	donor_gain	1.0000
9:4688510:TAGAG:T	acceptor_gain	1.0000
9:4688511:A:AG	acceptor_gain	1.0000
9:4688512:G:GG	acceptor_gain	1.0000
9:4688512:GA:G	acceptor_gain	1.0000
9:4697756:GAAA:G	acceptor_gain	1.0000
9:4697880:G:GG	donor_gain	1.0000
9:4701922:GA:G	donor_gain	1.0000
9:4701924:G:GG	donor_gain	1.0000
9:4679895:CCCAG:C	donor_loss	0.9900
9:4679896:CCAGG:C	donor_loss	0.9900
9:4679897:CAG:C	donor_loss	0.9900
9:4679898:AGG:A	donor_loss	0.9900
9:4679899:GGT:G	donor_loss	0.9900
9:4679901:T:G	donor_loss	0.9900
9:4684859:A:G	acceptor_gain	0.9900
9:4684871:A:AG	acceptor_gain	0.9900
9:4684873:CCA:C	acceptor_loss	0.9900
9:4684874:CA:C	acceptor_loss	0.9900
9:4684875:A:AG	acceptor_gain	0.9900
9:4684875:A:AT	acceptor_loss	0.9900
9:4684876:G:GG	acceptor_gain	0.9900
9:4684876:GATGT:G	acceptor_gain	0.9900
9:4685154:ATAAG:A	donor_loss	0.9900
9:4685156:AAGGT:A	donor_loss	0.9900
9:4685157:AGGT:A	donor_loss	0.9900
9:4685158:GG:G	donor_loss	0.9900
9:4685159:G:GC	donor_loss	0.9900
9:4685160:T:A	donor_loss	0.9900

AlphaMissense

2265 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:4697096:G:A	G170D	0.998
9:4697119:A:C	S178R	0.998
9:4697121:C:A	S178R	0.998
9:4697121:C:G	S178R	0.998
9:4697177:T:C	L197P	0.998
9:4697790:G:C	A220P	0.998
9:4697132:T:C	L182S	0.997
9:4697865:T:C	F245L	0.996
9:4697867:C:A	F245L	0.996
9:4697867:C:G	F245L	0.996
9:4697190:T:G	C201W	0.995
9:4697782:C:A	A217E	0.995
9:4697805:T:C	F225L	0.995
9:4697807:T:A	F225L	0.995
9:4697807:T:G	F225L	0.995
9:4697862:T:C	F244L	0.995
9:4697864:T:A	F244L	0.995
9:4697864:T:G	F244L	0.995
9:4697110:T:A	W175R	0.994
9:4697110:T:C	W175R	0.994
9:4697188:T:C	C201R	0.994
9:4697198:T:C	L204P	0.994
9:4697781:G:C	A217P	0.994
9:4697863:T:C	F244S	0.994
9:4701891:T:C	F259L	0.994
9:4701893:C:A	F259L	0.994
9:4701893:C:G	F259L	0.994
9:4684964:G:C	A74P	0.993
9:4688606:G:C	G170R	0.993
9:4697153:T:A	V189E	0.993

dbSNP variants (sampled 300 via entrez): RS1000001837 (9:4699720 C>G), RS1000046691 (9:4693438 G>C), RS1000087007 (9:4708754 T>A,C,G), RS1000098804 (9:4693596 G>A,T), RS1000110945 (9:4690511 C>T), RS1000314202 (9:4683101 T>A), RS1000351610 (9:4699486 G>A,T), RS1000442198 (9:4683062 T>A), RS1000474826 (9:4682967 A>G), RS1000520238 (9:4678762 A>G), RS1000654628 (9:4687747 G>T), RS1000727777 (9:4699118 A>G), RS1000744724 (9:4703182 A>G), RS1000776202 (9:4688036 C>T), RS1000795978 (9:4703582 G>C)

Disease associations

OMIM: gene MIM:610346 | disease phenotypes: MIM:158170

GenCC curated gene-disease

Mondo (1): chromosome 9p deletion syndrome (MONDO:0008013)

Orphanet (1): Monosomy 9p syndrome (Orphanet:261112)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST90002396_447	Mean reticulocyte volume	4.000000e-10
GCST90002406_317	Reticulocyte fraction of red cells	3.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C538024	Chromosome 9p Deletion Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
perfluorooctane sulfonic acid	decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
bisphenol F	affects cotreatment, decreases methylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
perfluorooctanoic acid	decreases expression	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	decreases expression	1
K 7174	increases expression	1
perfluorohexanesulfonic acid	decreases expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Ethanol	decreases expression	1
Benzo(a)pyrene	increases expression	1
Caffeine	decreases phosphorylation	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	increases expression, affects cotreatment	1
Phenobarbital	affects expression	1
Smoke	decreases expression	1
Thimerosal	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586400	Not specified	RECRUITING	Chromosome 9 P Minus Syndrome