DNLZ

Summary

DNLZ (DNL-type zinc finger, HGNC:33879) is a protein-coding gene on chromosome 9q34.3, encoding DNL-type zinc finger protein (Q5SXM8). May function as a co-chaperone towards HSPA9/mortalin which, by itself, is prone to self-aggregation. It is a selective cancer dependency (DepMap: 42.9% of cell lines).

Enables protein folding chaperone. Involved in chaperone-mediated protein complex assembly. Located in nucleoplasm. Is active in cytosol; mitochondrion; and nucleus.

Source: NCBI Gene 728489 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 1 total
• Cancer dependency (DepMap): dependent in 42.9% of screened cell lines
• MANE Select transcript: NM_001080849

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33879
Approved symbol	DNLZ
Name	DNL-type zinc finger
Location	9q34.3
Locus type	gene with protein product
Status	Approved
Aliases	RP11-413M3.2, ZIM17, bA413M3.2, TIMM15, HEP
Ensembl gene	ENSG00000213221
Ensembl biotype	protein_coding
OMIM	620797
Entrez	728489

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000371738, ENST00000371739, ENST00000893401

RefSeq mRNA: 1 — MANE Select: NM_001080849 NM_001080849

CCDS: CCDS35179

Canonical transcript exons

ENST00000371738 — 3 exons

Exon	Start	End
ENSE00001455968	136362989	136363128
ENSE00003992824	136363487	136363744
ENSE00003992836	136359483	136362180

Expression profiles

Bgee: expression breadth ubiquitous, 130 present calls, max score 81.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.4222 / max 46.0621, expressed in 1769 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
103145	7.4519	1749
103146	0.9703	647

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.31	gold quality
apex of heart	UBERON:0002098	80.02	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.66	gold quality
heart left ventricle	UBERON:0002084	75.71	gold quality
gastrocnemius	UBERON:0001388	72.35	gold quality
prefrontal cortex	UBERON:0000451	72.12	gold quality
heart	UBERON:0000948	71.90	gold quality
hindlimb stylopod muscle	UBERON:0004252	71.45	gold quality
muscle of leg	UBERON:0001383	71.44	gold quality
popliteal artery	UBERON:0002250	70.63	gold quality
tibial artery	UBERON:0007610	70.63	gold quality
body of pancreas	UBERON:0001150	69.60	gold quality
stromal cell of endometrium	CL:0002255	69.57	gold quality
right atrium auricular region	UBERON:0006631	69.50	gold quality
granulocyte	CL:0000094	69.05	gold quality
skeletal muscle tissue	UBERON:0001134	68.64	gold quality
left coronary artery	UBERON:0001626	68.60	gold quality
frontal cortex	UBERON:0001870	68.55	gold quality
ascending aorta	UBERON:0001496	68.24	gold quality
thoracic aorta	UBERON:0001515	68.17	gold quality
right coronary artery	UBERON:0001625	67.82	gold quality
ganglionic eminence	UBERON:0004023	67.10	gold quality
left uterine tube	UBERON:0001303	66.98	gold quality
cerebral cortex	UBERON:0000956	66.93	gold quality
temporal lobe	UBERON:0001871	66.63	gold quality
anterior cingulate cortex	UBERON:0009835	66.60	gold quality
amygdala	UBERON:0001876	66.58	gold quality
adult mammalian kidney	UBERON:0000082	66.55	gold quality
muscle layer of sigmoid colon	UBERON:0035805	66.50	gold quality
lower esophagus muscularis layer	UBERON:0035833	66.33	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

5 targeting DNLZ, 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-875-3P	99.63	69.47	2548
HSA-MIR-6128	99.33	67.83	1581
HSA-MIR-1237-3P	98.55	67.65	1423
HSA-MIR-654-3P	98.38	67.61	905
HSA-MIR-4433A-5P	96.79	65.01	599

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 42.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 5)

• These findings implicate a conserved histidine as critical for DNLZ regulation of mitochondrial HSPA9 catalytic activity. (PMID:21530495)
• DNLZ/HEP zinc-binding subdomain is critical for regulation of the mitochondrial chaperone HSPA9. Human DNLZ partially complements the growth of Deltazim17 Saccharomyces cerevisiae. (PMID:22162012)
• The results indicate that hHep1 shares some structural similarities with the yeast ortholog despite the low identity and functional differences. (PMID:23462535)
• New insights on human Hsp70-escort protein 1: Chaperone activity, interaction with liposomes, cellular localizations and HSPA’s self-assemblies remodeling. (PMID:33857516)
• Human HSP70-escort protein 1 (hHep1) interacts with negatively charged lipid bilayers and cell membranes. (PMID:38001371)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnlz	ENSDARG00000068655
mus_musculus	Dnlz	ENSMUSG00000075467
rattus_norvegicus	Dnlz	ENSRNOG00000018791
drosophila_melanogaster	CG12379	FBGN0030676
drosophila_melanogaster	CG8206	FBGN0030679
caenorhabditis_elegans		WBGENE00018723

Protein

Protein identifiers

DNL-type zinc finger protein — Q5SXM8 (reviewed: Q5SXM8)

Alternative names: Hsp70-escort protein 1, mtHsp70-escort protein

All UniProt accessions (2): Q5SXM7, Q5SXM8

UniProt curated annotations — full annotation on UniProt →

Function. May function as a co-chaperone towards HSPA9/mortalin which, by itself, is prone to self-aggregation.

Subunit / interactions. Oligomerizes in a concentration-dependent fashion. Interacts with HSPA9.

Subcellular location. Mitochondrion.

RefSeq proteins (1): NP_001074318* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007853	Znf_DNL-typ	Domain
IPR024158	Mt_import_TIM15	Family

Pfam: PF05180

UniProt features (10 total): binding site 4, sequence variant 2, transit peptide 1, chain 1, zinc finger region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5SXM8-F1	68.20	0.25

Functional residue map

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

Ligand- & substrate-binding residues (4): 75; 78; 100; 103

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 74 (showing top): GOBP_CHAPERONE_MEDIATED_PROTEIN_COMPLEX_ASSEMBLY, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_PROTEIN_MATURATION, GOBP_PROTEIN_STABILIZATION, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, GOBP_PROTEIN_FOLDING, GOBP_REGULATION_OF_PROTEIN_STABILITY, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_PROTEIN_TRANSMEMBRANE_TRANSPORT, GOBP_PROTEIN_LOCALIZATION_TO_MITOCHONDRION, GOBP_PROTEIN_IMPORT_INTO_MITOCHONDRIAL_MATRIX, IVANOVA_HEMATOPOIESIS_INTERMEDIATE_PROGENITOR, GOBP_TRANSMEMBRANE_TRANSPORT, SANSOM_APC_TARGETS, SANSOM_APC_TARGETS_REQUIRE_MYC

GO Biological Process (4): protein folding (GO:0006457), protein import into mitochondrial matrix (GO:0030150), protein stabilization (GO:0050821), chaperone-mediated protein complex assembly (GO:0051131)

GO Molecular Function (4): zinc ion binding (GO:0008270), protein folding chaperone (GO:0044183), protein-folding chaperone binding (GO:0051087), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), mitochondrion (GO:0005739), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
cytoplasm	2
cellular process	1
protein maturation	1
protein transmembrane import into intracellular organelle	1
protein localization to mitochondrion	1
import into the mitochondrion	1
mitochondrial protein import pathway	1
regulation of protein stability	1
protein-containing complex assembly	1
transition metal ion binding	1
molecular_function	1
protein folding	1
protein binding	1
cation binding	1
nuclear lumen	1

Protein interactions and networks

STRING

744 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNLZ	HSPA9	P30036	821
DNLZ	TIMM44	O43615	622
DNLZ	GRPEL1	Q9HAV7	564
DNLZ	TIMM13	P62206	507
DNLZ	TMEM69	Q5SWH9	479
DNLZ	PAM16	Q9Y3D7	469
DNLZ	GRPEL2	Q8TAA5	461
DNLZ	TIMM17A	Q99595	456
DNLZ	COQ4	Q9Y3A0	433
DNLZ	DNAJC19	Q96DA6	422
DNLZ	TOMM40	O96008	406
DNLZ	DNAJA3	Q96EY1	402
DNLZ	TIMM50	Q3ZCQ8	400
DNLZ	ASDURF	L0R819	391
DNLZ	DRAP1	Q14919	378

IntAct

56 interactions, top by confidence:

A	B	Type	Score
MRPL37	HSPD1	psi-mi:“MI:0914”(association)	0.710
COX7A2	COX6B1	psi-mi:“MI:0914”(association)	0.640
ACTBL2	POTEF	psi-mi:“MI:0914”(association)	0.530
ATPAF2	NDUFAB1	psi-mi:“MI:0914”(association)	0.530
HUS1B	ZBTB14	psi-mi:“MI:0914”(association)	0.530
HSPA9	DNAJC13	psi-mi:“MI:0914”(association)	0.530
LDHAL6B	MTIF2	psi-mi:“MI:0914”(association)	0.530
ATG7	GFER	psi-mi:“MI:0914”(association)	0.530
SLC25A22	DNLZ	psi-mi:“MI:0914”(association)	0.530
PDK3	PDHX	psi-mi:“MI:0914”(association)	0.530
ECHDC2	NDUFS6	psi-mi:“MI:0914”(association)	0.530
ADIPOQ	C1QL1	psi-mi:“MI:0914”(association)	0.530
SGK3	CDC37	psi-mi:“MI:0914”(association)	0.530
CCL14	DNLZ	psi-mi:“MI:0914”(association)	0.530
NDUFV2	NDUFS8	psi-mi:“MI:0914”(association)	0.530
SPCS3	ENTPD6	psi-mi:“MI:0914”(association)	0.530
AURKAIP1	NRDC	psi-mi:“MI:0914”(association)	0.480
COX7A2	COX4I1	psi-mi:“MI:0914”(association)	0.480
PLA1A	DNLZ	psi-mi:“MI:0915”(physical association)	0.400
SUCLA2	GTPBP10	psi-mi:“MI:0914”(association)	0.350
ECHDC2		psi-mi:“MI:0914”(association)	0.350
PDK3		psi-mi:“MI:0914”(association)	0.350

BioGRID (58): DNLZ (Affinity Capture-MS), DNLZ (Affinity Capture-MS), DNLZ (Affinity Capture-MS), DNLZ (Affinity Capture-MS), DNLZ (Affinity Capture-MS), DNLZ (Affinity Capture-MS), DNLZ (Affinity Capture-MS), DNLZ (Affinity Capture-MS), DNLZ (Affinity Capture-MS), DNLZ (Affinity Capture-MS), DNLZ (Affinity Capture-MS), DNLZ (Affinity Capture-MS), DNLZ (Affinity Capture-MS), DNLZ (Affinity Capture-MS), DNLZ (Affinity Capture-MS)

ESM2 similar proteins: A1L1P7, A2A5E6, A6NNL5, A7YVI8, A8NN94, B2RZ39, C1BJQ3, O14320, O14464, O76454, O94690, P0DKI0, P0DKI1, P42797, P52505, Q04598, Q05B87, Q0IH40, Q1ECT8, Q1K7P9, Q1LWG3, Q4G0I0, Q4R1S9, Q4R319, Q4V7Q1, Q5BKU9, Q5R7Q6, Q5RB32, Q5RFR4, Q5SXM8, Q5ZLC1, Q6H611, Q6MG11, Q6RUT7, Q7S4E7, Q7YRF4, Q84WZ8, Q8JMY3, Q8K341, Q942X4

Diamond homologs: A1L1P7, A6ZSH0, B3LPE4, B5VQB0, P42844, Q09759, Q0IH40, Q5SXM8, Q9D113

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 68 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
Complex I biogenesis	5	17.6×	9e-04
Respiratory electron transport	8	16.2×	8e-06
Mitochondrial protein degradation	6	14.6×	5e-04
TP53 Regulates Metabolic Genes	5	13.8×	2e-03
Aerobic respiration and respiratory electron transport	6	11.3×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

294 predictions. Top by Δscore:

Variant	Effect	Δscore
9:136362985:TCAC:T	donor_loss	1.0000
9:136362986:CACC:C	donor_loss	1.0000
9:136362987:A:C	donor_loss	1.0000
9:136362988:C:CA	donor_loss	1.0000
9:136362988:CCT:C	donor_gain	1.0000
9:136362994:C:A	donor_gain	1.0000
9:136363375:T:TA	donor_gain	1.0000
9:136362176:TATTT:T	acceptor_gain	0.9900
9:136362178:TTT:T	acceptor_gain	0.9900
9:136362181:C:CC	acceptor_gain	0.9900
9:136362189:C:CT	acceptor_gain	0.9900
9:136362993:T:TA	donor_gain	0.9900
9:136363128:CCTGG:C	acceptor_loss	0.9900
9:136363129:CTGGC:C	acceptor_loss	0.9900
9:136363131:GGCT:G	acceptor_loss	0.9900
9:136363132:GCTGG:G	acceptor_loss	0.9900
9:136363133:CT:C	acceptor_loss	0.9900
9:136363134:T:A	acceptor_loss	0.9900
9:136363482:CCTA:C	donor_loss	0.9900
9:136363483:CTA:C	donor_loss	0.9900
9:136363484:TA:T	donor_loss	0.9900
9:136363486:C:CT	donor_loss	0.9900
9:136362179:TT:T	acceptor_gain	0.9800
9:136362190:A:T	acceptor_gain	0.9800
9:136362987:A:AC	donor_gain	0.9800
9:136362988:C:CC	donor_gain	0.9800
9:136362990:T:TA	donor_gain	0.9800
9:136363124:CAGAC:C	acceptor_gain	0.9800
9:136363133:C:CC	acceptor_gain	0.9800
9:136363372:C:CA	donor_gain	0.9800

AlphaMissense

1118 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:136363009:G:C	F116L	0.996
9:136363009:G:T	F116L	0.996
9:136363011:A:G	F116L	0.996
9:136363031:A:T	I109N	0.992
9:136363028:G:T	A110D	0.990
9:136363067:A:T	I97N	0.989
9:136363086:A:C	Y91D	0.988
9:136363010:A:G	F116S	0.987
9:136363100:A:G	I86T	0.987
9:136363070:A:T	V96D	0.986
9:136362166:A:G	I128T	0.985
9:136363010:A:C	F116C	0.985
9:136363038:G:C	H107D	0.985
9:136363049:C:G	C103S	0.985
9:136363050:A:T	C103S	0.985
9:136363059:A:G	C100R	0.985
9:136362175:A:T	I125N	0.983
9:136363025:T:A	D111V	0.983
9:136363036:A:C	H107Q	0.982
9:136363036:A:T	H107Q	0.982
9:136363100:A:T	I86N	0.981
9:136363024:G:C	D111E	0.980
9:136363024:G:T	D111E	0.980
9:136363014:A:G	W115R	0.979
9:136363014:A:T	W115R	0.979
9:136363026:C:G	D111H	0.979
9:136363100:A:C	I86S	0.979
9:136363029:C:G	A110P	0.977
9:136363086:A:G	Y91H	0.977
9:136363086:A:T	Y91N	0.976

dbSNP variants (sampled 300 via entrez): RS1000218738 (9:136362041 G>A), RS1000647923 (9:136362675 G>A), RS1000708650 (9:136363740 G>A,C), RS1000747664 (9:136359534 G>A), RS1000811409 (9:136359727 C>T), RS1000829251 (9:136363608 G>A,C), RS1000955173 (9:136360511 G>A), RS1001389471 (9:136360362 A>C,G), RS1001777497 (9:136361584 T>C,G), RS1001818367 (9:136361727 C>T), RS1001997186 (9:136363757 C>G,T), RS1002116342 (9:136360714 C>T), RS1002119545 (9:136362298 T>A,C,G), RS1002254165 (9:136359410 G>A), RS1002284277 (9:136363966 C>T)

Disease associations

OMIM: gene MIM:620797 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST004131_21	Inflammatory bowel disease	5.000000e-36
GCST004132_11	Crohn’s disease	6.000000e-30
GCST004133_17	Ulcerative colitis	2.000000e-16
GCST004184_1	Lung function (FVC)	9.000000e-10
GCST006676_1	Peak insulin response (insulin secretion adjusted)	3.000000e-06
GCST007429_137	Lung function (FVC)	9.000000e-09
GCST007432_184	FEV1	4.000000e-07
GCST008643_2	Joint damage in rheumatoid arthritis	1.000000e-06
GCST90020028_31	Hip circumference adjusted for BMI	1.000000e-09
GCST90020028_32	Hip circumference adjusted for BMI	8.000000e-10

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004312	vital capacity
EFO:0008000	peak insulin response measurement
EFO:0004314	forced expiratory volume
EFO:0005413	joint damage measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression, decreases methylation	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
Air Pollutants	decreases expression, increases abundance, increases expression	2
Valproic Acid	affects expression, decreases expression, increases methylation	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
trichostatin A	affects expression	1
ICG 001	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases response to substance, decreases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Benzo(a)pyrene	increases expression	1
Quercetin	decreases phosphorylation	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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