ZFR

Summary

ZFR (zinc finger RNA binding protein, HGNC:17277) is a protein-coding gene on chromosome 5p13.3, encoding Zinc finger RNA-binding protein (Q96KR1). Involved in postimplantation and gastrulation stages of development. It is a selective cancer dependency (DepMap: 17.7% of cell lines).

This gene encodes an RNA-binding protein characterized by its DZF (domain associated with zinc fingers) domain. The encoded protein may play a role in the nucleocytoplasmic shuttling of another RNA-binding protein, Staufen homolog 2, in neurons. Expression of this gene is regulated through alternative polyadenylation that mediates differential microRNA targeting. Elevated expression of this gene has been observed in human patients with pancreatic cancer and knockdown of this gene may result in reduced viability and invasion of pancreatic cancer cells.

Source: NCBI Gene 51663 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive spastic paraplegia type 71 (Supportive, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 315 total
• Phenotypes (HPO): 13
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 17.7% of screened cell lines
• MANE Select transcript: NM_016107

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17277
Approved symbol	ZFR
Name	zinc finger RNA binding protein
Location	5p13.3
Locus type	gene with protein product
Status	Approved
Aliases	ZFR1, SPG71
Ensembl gene	ENSG00000056097
Ensembl biotype	protein_coding
OMIM	615635
Entrez	51663

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 9 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000265069, ENST00000502988, ENST00000505204, ENST00000505366, ENST00000507465, ENST00000510369, ENST00000514356, ENST00000890167, ENST00000890168, ENST00000890169, ENST00000890170, ENST00000890171, ENST00000927191, ENST00000956811, ENST00000956812

RefSeq mRNA: 1 — MANE Select: NM_016107 NM_016107

CCDS: CCDS34139

Canonical transcript exons

ENST00000265069 — 20 exons

Exon	Start	End
ENSE00000735172	32385508	32385649
ENSE00000999295	32397219	32397338
ENSE00000999296	32400007	32400203
ENSE00000999298	32395159	32395304
ENSE00000999299	32390275	32390437
ENSE00001380312	32406774	32407021
ENSE00001380970	32403906	32404097
ENSE00001504843	32387549	32387699
ENSE00001504844	32388469	32388674
ENSE00001504845	32403106	32403397
ENSE00002054790	32444622	32444740
ENSE00002073168	32354350	32355939
ENSE00003474536	32414969	32415187
ENSE00003546103	32364164	32364275
ENSE00003563739	32363948	32364045
ENSE00003609706	32417648	32417792
ENSE00003639103	32379115	32379210
ENSE00003673804	32444229	32444328
ENSE00003675371	32419821	32420103
ENSE00003680267	32380075	32380172

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 98.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 53.0930 / max 542.7415, expressed in 1821 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
61190	30.3140	1811
61191	18.8335	1804
61189	1.0454	580
61179	0.6159	138
61188	0.5629	213
61180	0.5536	269
61187	0.4941	241
61176	0.3161	69
61178	0.1781	47
61177	0.1249	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
CA1 field of hippocampus	UBERON:0003881	98.58	gold quality
germinal epithelium of ovary	UBERON:0001304	98.49	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.35	gold quality
endothelial cell	CL:0000115	98.18	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.15	gold quality
ventricular zone	UBERON:0003053	97.87	gold quality
tibia	UBERON:0000979	97.85	gold quality
middle frontal gyrus	UBERON:0002702	97.84	gold quality
parotid gland	UBERON:0001831	97.76	gold quality
postcentral gyrus	UBERON:0002581	97.75	gold quality
entorhinal cortex	UBERON:0002728	97.71	gold quality
cranial nerve II	UBERON:0000941	97.58	gold quality
superior frontal gyrus	UBERON:0002661	97.55	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.50	gold quality
choroid plexus epithelium	UBERON:0003911	97.47	gold quality
parietal lobe	UBERON:0001872	97.46	gold quality
inferior olivary complex	UBERON:0002127	97.44	gold quality
cortical plate	UBERON:0005343	97.37	gold quality
lateral globus pallidus	UBERON:0002476	97.33	gold quality
ganglionic eminence	UBERON:0004023	97.25	gold quality
paraflocculus	UBERON:0005351	97.25	gold quality
cartilage tissue	UBERON:0002418	97.19	gold quality
middle temporal gyrus	UBERON:0002771	97.19	gold quality
cerebellar vermis	UBERON:0004720	97.11	gold quality
frontal pole	UBERON:0002795	97.10	gold quality
corpus callosum	UBERON:0002336	97.02	gold quality
orbitofrontal cortex	UBERON:0004167	97.00	gold quality
pigmented layer of retina	UBERON:0001782	96.98	gold quality
retina	UBERON:0000966	96.95	gold quality
epithelium of nasopharynx	UBERON:0001951	96.86	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

204 targeting ZFR, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 17.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 9)

• polyadenylation allows differential negative feedback of human miRNA miR-579 on its host gene ZFR (PMID:25799583)
• ZFR expression is tightly controlled during macrophage development; monocytes express truncated ZFR isoforms, while macrophages induce full-length ZFR to modulate macrophage-specific alternative splicing. (PMID:29559679)
• Identified a new circRNA, circZFR, that was significantly upregulated in papillary thyroid carcinoma (PTC). CircZFR could promote C8orf4 expression via serving as a competing endogenous RNA of miR-1261 in PTC cells. Rescue assays indicated that restoration of C8orf4 significantly attenuated the inhibitory effects of circZFR knockdown on PTC cell proliferation, migration and invasion. (PMID:29842886)
• ZFR was confirmed as a target gene of miR-141-3p and negatively correlated with miR-141-3p expression in non-small cell lung cancer tissues. (PMID:30611568)
• Hyperglycaemia elevates ZFR in vivo and in vitro. ZFR can promote the proliferation and migration of human retinal microvascular endothelial cells cultured in high glucose condition. (PMID:30914198)
• overexpression of ZFR in CRC and liver cancer cells led to accelerated tumor development. Consistently, knockdown of ZFR resulted in significantly decelerated tumor development. (PMID:31010678)
• Circular RNA circZFR Promotes Hepatocellular Carcinoma Progression by Regulating miR-375/HMGA2 Axis. (PMID:33433801)
• The circular RNA circZFR phosphorylates Rb promoting cervical cancer progression by regulating the SSBP1/CDK2/cyclin E1 complex. (PMID:33516252)
• Circulating RNA ZFR promotes hepatocellular carcinoma cell proliferation and epithelial-mesenchymal transition process through miR-624-3p/WEE1 axis. (PMID:37516591)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	zfr	ENSDARG00000027109
mus_musculus	Zfr	ENSMUSG00000022201
rattus_norvegicus	Zfr	ENSRNOG00000011627
drosophila_melanogaster	loqs	FBGN0032515
drosophila_melanogaster	CG12493	FBGN0035571
drosophila_melanogaster	blanks	FBGN0035608
drosophila_melanogaster	Zn72D	FBGN0263603
caenorhabditis_elegans	zfr-1	WBGENE00022388

Paralogs (14): STAU2 (ENSG00000040341), ADAT1 (ENSG00000065457), ZFR2 (ENSG00000105278), STAU1 (ENSG00000124214), ILF3 (ENSG00000129351), TARBP2 (ENSG00000139546), ADAD2 (ENSG00000140955), ILF2 (ENSG00000143621), ADAR (ENSG00000160710), ADAD1 (ENSG00000164113), STRBP (ENSG00000165209), PRKRA (ENSG00000180228), ADARB2 (ENSG00000185736), ADARB1 (ENSG00000197381)

Protein

Protein identifiers

Zinc finger RNA-binding protein — Q96KR1 (reviewed: Q96KR1)

Alternative names: M-phase phosphoprotein homolog

All UniProt accessions (2): Q96KR1, H0Y8W1

UniProt curated annotations — full annotation on UniProt →

Function. Involved in postimplantation and gastrulation stages of development. Involved in the nucleocytoplasmic shuttling of STAU2. Binds to DNA and RNA.

Subunit / interactions. Found in a cytoplasmic RNP complex with STAU2. Interacts with STAU2. Does not interact with STAU1.

Subcellular location. Nucleus. Cytoplasm. Cytoplasmic granule. Chromosome.

Tissue specificity. Expressed in lung, liver, lymphocytes, heart, pancreas, placenta, brain and kidney.

RefSeq proteins (1): NP_057191* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003604	Matrin/U1-like-C_Znf_C2H2	Domain
IPR006561	DZF_dom	Domain
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR043519	NT_sf	Homologous_superfamily
IPR049401	DZF_dom_N	Domain
IPR049402	DZF_dom_C	Domain

Pfam: PF07528, PF12874, PF20965

UniProt features (28 total): sequence conflict 7, region of interest 6, compositionally biased region 4, modified residue 3, cross-link 3, sequence variant 3, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96KR1-F1	62.11	0.27

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 (6): 509, 516, 1054, 509, 541, 623

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 199 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, ACTGCAG_MIR173P, MARTINEZ_RB1_TARGETS_UP, WANG_LMO4_TARGETS_DN, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, DOANE_RESPONSE_TO_ANDROGEN_DN, BROWNE_HCMV_INFECTION_14HR_DN, TCF11_01, TGANTCA_AP1_C, CYTAGCAAY_UNKNOWN, DODD_NASOPHARYNGEAL_CARCINOMA_UP, SENESE_HDAC1_TARGETS_UP, GCM_NF2, CUI_TCF21_TARGETS_2_DN, CTTTGTA_MIR524

GO Biological Process (0):

GO Molecular Function (7): DNA binding (GO:0003677), RNA binding (GO:0003723), double-stranded RNA binding (GO:0003725), single-stranded RNA binding (GO:0003727), zinc ion binding (GO:0008270), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), chromosome (GO:0005694), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleic acid binding	2
RNA binding	2
binding	2
transition metal ion binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1958 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZFR	ZPR1	O75312	551
ZFR	MTMR12	Q9C0I1	467
ZFR	STAU2	Q9NUL3	460
ZFR	SPG21	Q9NZD8	445
ZFR	RBM7	Q9Y580	417
ZFR	ARSI	Q5FYB1	406
ZFR	ZHX3	Q9H4I2	403
ZFR	TP53BP1	Q12888	399
ZFR	NPY5R	Q15761	393
ZFR	ZHX2	Q9Y6X8	385
ZFR	ZFR2	Q9UPR6	384
ZFR	AP5Z1	O43299	382
ZFR	AP4S1	Q9Y587	379
ZFR	PTPN14	Q15678	378
ZFR	GGA1	Q9UJY5	378

IntAct

231 interactions, top by confidence:

A	B	Type	Score
	TOMM70	psi-mi:“MI:0914”(association)	0.980
HNRNPC	KPNA3	psi-mi:“MI:0914”(association)	0.850
LARP7	CCNT1	psi-mi:“MI:0914”(association)	0.850
FBL	NOP56	psi-mi:“MI:0914”(association)	0.800
HNRNPCL1	HNRNPC	psi-mi:“MI:0914”(association)	0.670
IGF2BP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
SNRNP70	GEMIN2	psi-mi:“MI:0914”(association)	0.640
HNRNPD	HNRNPDL	psi-mi:“MI:0914”(association)	0.560
FOXP3	FOXP2	psi-mi:“MI:0914”(association)	0.530
BCOR	CBX4	psi-mi:“MI:0914”(association)	0.530
ZNF169	ZNF316	psi-mi:“MI:0914”(association)	0.530
ILF2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
ZYX	TBC1D10B	psi-mi:“MI:0914”(association)	0.530
N	HNRNPDL	psi-mi:“MI:0914”(association)	0.530
FHL2	CNOT1	psi-mi:“MI:0914”(association)	0.530
RPS3	ZNF316	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
ELAVL2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
PAIP2B	CASC3	psi-mi:“MI:0914”(association)	0.530
ILF2	RRP8	psi-mi:“MI:0914”(association)	0.530
FBXW11	AHCYL1	psi-mi:“MI:0914”(association)	0.530
HNRNPA1	PTCD1	psi-mi:“MI:0914”(association)	0.530
SNRPC	SNRPGP15	psi-mi:“MI:0914”(association)	0.530
GSPT2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
RPS2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530

BioGRID (386): ZFR (Affinity Capture-RNA), ZFR (Affinity Capture-RNA), ZFR (Affinity Capture-MS), ZFR (Affinity Capture-MS), ZFR (Affinity Capture-MS), ZFR (Affinity Capture-MS), ZFR (Affinity Capture-MS), ZFR (Affinity Capture-MS), ZFR (Affinity Capture-MS), ZFR (Affinity Capture-MS), ZFR (Affinity Capture-MS), ZFR (Affinity Capture-MS), ZFR (Affinity Capture-MS), ZFR (Affinity Capture-MS), DNMT1 (Co-fractionation)

ESM2 similar proteins: A0JMV4, A1A5G2, A4IGK4, A5D7H2, B2GV05, E1C1R4, O88532, O94888, P52756, P54198, P58405, P79987, Q01826, Q13033, Q13123, Q14161, Q1RMU5, Q562A2, Q5NVI3, Q5R660, Q5RCR8, Q5REX3, Q5REY7, Q5SRX1, Q5U231, Q5U252, Q60611, Q61666, Q66H91, Q66HG8, Q6GPM1, Q6NT76, Q80YA9, Q8BIE6, Q8BJA3, Q8BY87, Q8K2D3, Q8VHE0, Q8VI24, Q8WXI2

Diamond homologs: O88532, Q08E27, Q0VD35, Q12906, Q562A2, Q5R6Y5, Q5REX3, Q5U231, Q5ZIL4, Q6DCD0, Q6DD04, Q6GL57, Q6GPM1, Q6NXA4, Q6PCR6, Q7TP98, Q91550, Q91WM1, Q96KR1, Q96SI9, Q9H898, Q9JIL3, Q9JKU6, Q9UPR6, Q9Z1X4, B8GAM6, P51400, P78563, P97616, Q12905, Q5RFJ1, Q6NZ06, Q6P8G1, Q7ZW47, Q8CJ67, Q91ZS8, Q9CXY6, Q9JI20, Q9NII1, Q9NS39

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 220 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
SARS-CoV-1 modulates host translation machinery	9	19.2×	3e-08
Eukaryotic Translation Initiation	8	17.0×	4e-07
Cap-dependent Translation Initiation	8	17.0×	4e-07
Nonsense-Mediated Decay (NMD)	10	16.1×	2e-08
SARS-CoV-2 modulates host translation machinery	10	15.4×	3e-08
Eukaryotic Translation Elongation	8	15.4×	7e-07
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	8	15.0×	9e-07
Influenza Viral RNA Transcription and Replication	9	13.4×	4e-07

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of cytoplasmic translation	7	35.6×	8e-08
alternative mRNA splicing, via spliceosome	7	24.2×	1e-06
negative regulation of translation	13	13.1×	6e-09
cytoplasmic translation	13	12.3×	9e-09
mRNA export from nucleus	8	12.1×	3e-05
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	5	12.0×	3e-03
regulation of alternative mRNA splicing, via spliceosome	9	11.3×	1e-05
RNA processing	10	11.2×	2e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	155
Likely benign	124
Benign	10

Top pathogenic / likely-pathogenic (0)

SpliceAI

3427 predictions. Top by Δscore:

Variant	Effect	Δscore
5:32355940:C:CC	acceptor_gain	1.0000
5:32363943:AGTAC:A	donor_loss	1.0000
5:32363945:TA:T	donor_loss	1.0000
5:32363947:CCTG:C	donor_loss	1.0000
5:32364042:CTAC:C	acceptor_gain	1.0000
5:32364043:TAC:T	acceptor_gain	1.0000
5:32364046:C:CC	acceptor_gain	1.0000
5:32364046:CT:C	acceptor_loss	1.0000
5:32364049:C:CT	acceptor_gain	1.0000
5:32364050:A:T	acceptor_gain	1.0000
5:32364052:C:CT	acceptor_gain	1.0000
5:32364053:A:T	acceptor_gain	1.0000
5:32364056:C:CT	acceptor_gain	1.0000
5:32364059:C:CT	acceptor_gain	1.0000
5:32364059:C:T	acceptor_gain	1.0000
5:32364061:C:CT	acceptor_gain	1.0000
5:32379107:CTA:C	donor_gain	1.0000
5:32379110:CTT:C	donor_loss	1.0000
5:32379111:TTA:T	donor_loss	1.0000
5:32379112:TA:T	donor_loss	1.0000
5:32379113:A:AC	donor_gain	1.0000
5:32379113:A:T	donor_loss	1.0000
5:32379113:AC:A	donor_gain	1.0000
5:32379114:C:CC	donor_gain	1.0000
5:32379114:CC:C	donor_gain	1.0000
5:32379114:CCCAG:C	donor_gain	1.0000
5:32379206:CTAGC:C	acceptor_gain	1.0000
5:32379210:CCT:C	acceptor_gain	1.0000
5:32379211:C:CC	acceptor_gain	1.0000
5:32379211:C:T	acceptor_gain	1.0000

AlphaMissense

6955 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:32355916:G:C	F1023L	1.000
5:32355916:G:T	F1023L	1.000
5:32355918:A:G	F1023L	1.000
5:32355926:A:G	L1020P	1.000
5:32355929:C:G	R1019T	1.000
5:32363973:C:G	R1007P	1.000
5:32364020:A:C	C991W	1.000
5:32364021:C:T	C991Y	1.000
5:32364022:A:G	C991R	1.000
5:32364179:C:A	G978W	1.000
5:32379115:C:A	W945C	1.000
5:32379115:C:G	W945C	1.000
5:32379117:A:G	W945R	1.000
5:32379117:A:T	W945R	1.000
5:32379135:A:G	W939R	1.000
5:32379135:A:T	W939R	1.000
5:32379155:A:G	L932P	1.000
5:32379171:G:T	R927S	1.000
5:32380078:G:C	F912L	1.000
5:32380078:G:T	F912L	1.000
5:32380079:A:C	F912C	1.000
5:32380079:A:G	F912S	1.000
5:32380080:A:G	F912L	1.000
5:32380081:C:A	W911C	1.000
5:32380081:C:G	W911C	1.000
5:32380083:A:G	W911R	1.000
5:32380083:A:T	W911R	1.000
5:32380084:C:A	K910N	1.000
5:32380084:C:G	K910N	1.000
5:32380085:T:A	K910M	1.000

dbSNP variants (sampled 300 via entrez): RS1000007444 (5:32390340 G>T), RS1000039354 (5:32431291 T>C), RS1000055073 (5:32415350 T>C), RS1000131702 (5:32422330 T>C), RS1000157793 (5:32438196 A>C), RS1000167093 (5:32356047 A>G), RS1000168655 (5:32425385 A>G), RS1000196667 (5:32355688 CA>C), RS1000235298 (5:32409816 T>A,C), RS1000290232 (5:32377220 C>T), RS1000315190 (5:32383212 C>T), RS1000406068 (5:32376782 T>A), RS1000447330 (5:32368247 C>A,T), RS1000493472 (5:32418942 G>A,C), RS1000506756 (5:32426810 C>T)

Disease associations

OMIM: gene MIM:615635 | disease phenotypes: MIM:303350

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive spastic paraplegia type 71	Supportive	Autosomal recessive
hereditary spastic paraplegia	Limited	Autosomal recessive

Mondo (3): hereditary spastic paraplegia (MONDO:0019064), intellectual disability (MONDO:0001071), autosomal recessive spastic paraplegia type 71 (MONDO:0018423)

Orphanet (3): Pure or complex autosomal recessive spastic paraplegia (Orphanet:320346), Hereditary spastic paraplegia (Orphanet:685), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

13 total (13 of 13 shown, HPO-id order):

HPO	Term
HP:0001256	Mild intellectual disability
HP:0001263	Global developmental delay
HP:0001347	Hyperreflexia
HP:0002061	Lower limb spasticity
HP:0002064	Spastic gait
HP:0002079	Hypoplasia of the corpus callosum
HP:0002378	Hand tremor
HP:0003457	EMG abnormality
HP:0003487	Babinski sign
HP:0007020	Progressive spastic paraplegia
HP:0009830	Peripheral neuropathy
HP:0012447	Abnormal myelination
HP:0100022	Abnormality of movement

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009391_1729	Metabolite levels	9.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010375	phosphatidylcholine 34:1 measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D015419	Spastic Paraplegia, Hereditary	C10.500.300.820; C10.574.500.495.820; C10.668.829.800.300.820; C16.131.666.300.820; C16.320.400.375.820

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067338 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.83	Kd	148.1	nM	CHEMBL5653589
6.83	ED50	148.1	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149811: Binding affinity to human ZFR incubated for 45 mins by Kinobead based pull down assay	kd	0.1481	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression, affects expression	4
Valproic Acid	affects cotreatment, increases expression, decreases expression	4
sodium arsenite	decreases expression, increases expression	3
bisphenol F	increases expression, affects cotreatment	2
methylmercuric chloride	increases expression	2
bisphenol A	affects expression, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
TAK-243	increases sumoylation	1
geldanamycin	increases expression	1
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
deoxynivalenol	increases expression	1
sodium arsenate	decreases expression	1
testosterone undecanoate	affects cotreatment, decreases expression	1
decabromobiphenyl ether	increases expression	1
terbufos	decreases methylation	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
tetrabromobisphenol A	decreases expression	1
alpha-cobratoxin	decreases expression, decreases reaction	1
nivalenol	increases expression	1
beta-methylcholine	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
torcetrapib	increases expression	1
abrine	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652853	Binding	Binding affinity to human ZFR incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3LL	Abcam HEK293T ZFR KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07542548	PHASE4	COMPLETED	D-Cycloserine for Serine Palmitoyltransferase Inhibition
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT03961906	PHASE2	COMPLETED	Physiotherapy in Hereditary Spastic Paraplegia
NCT04768166	PHASE2	COMPLETED	Testing Miglustat Administration in Subjects With Spastic Paraplegia 11
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT06117020	PHASE1	COMPLETED	Single and Multiple Ascending Dose Study of MTR-601 in Healthy Individuals
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT02604186	PHASE2/PHASE3	COMPLETED	Effects of Botulinum Toxin Injections in Patients With Hereditary Spastic Paraplegia
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT06948019	PHASE1/PHASE2	NOT_YET_RECRUITING	Safety and Efficacy of AAV9/AP4B1 (BFB-101) For Patients With AP4B1-related Hereditary Spastic Paraplegia Type 47 (SPG47)
NCT06478238	EARLY_PHASE1	RECRUITING	Calcium Folinate Treatment of Spastic Paraplegia 56
NCT00023075	Not specified	COMPLETED	Nuclear Magnetic Spectroscopy Imaging to Evaluate Primary Lateral Sclerosis, Hereditary Spastic Paraplegia and Amyotrophic Lateral Sclerosis
NCT00136630	Not specified	COMPLETED	Natural History, Genetic Bases and Phenotype-genotype Correlations in Autosomal Dominant Spinocerebellar Degenerations
NCT00140829	Not specified	COMPLETED	SPATAX: Clinical and Genetic Analysis of Cerebellar Ataxias and Spastic Paraplegias
NCT00677768	Not specified	COMPLETED	Validation of Biomarkers in Amyotrophic Lateral Sclerosis (ALS)
NCT01568658	Not specified	ACTIVE_NOT_RECRUITING	Genetic and Physical Study of Childhood Nerve and Muscle Disorders
NCT02327845	Not specified	ENROLLING_BY_INVITATION	Phenotype, Genotype & Biomarkers in ALS and Related Disorders
NCT02852278	Not specified	COMPLETED	A Patient Centric Motor Neuron Disease Activities of Daily Living Scale
NCT02859428	Not specified	TERMINATED	Disease Natural History and Biomarkers of SPG3A, SPG4A, and SPG31
NCT03104088	Not specified	COMPLETED	Studying Cognition in SPG4
NCT03206190	Not specified	RECRUITING	The preSPG4 Study - Studying the Prodromal and Early Phase of SPG4
NCT03627416	Not specified	COMPLETED	Repetitive Transcranial Magnetic Stimulation as Therapy in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy
NCT03981276	Not specified	RECRUITING	Phenotypes, Biomarkers and Pathophysiology in Hereditary Spastic Paraplegias and Related Disorders
NCT04006418	Not specified	RECRUITING	A Registered Cohort Study on Spastic Paraplegia
NCT04180098	Not specified	COMPLETED	Improving Gait Adaptability in Hereditary Spastic Paraplegia
NCT04256681	Not specified	COMPLETED	SNAP: Measurement of the Subjective Perception of the Symptom in Hereditary Spastic Paraparesis (HSP)
NCT04712812	Not specified	RECRUITING	Registry and Natural History Study for Early Onset Hereditary Spastic Paraplegia
NCT04875416	Not specified	ACTIVE_NOT_RECRUITING	Phenotype, Genotype and Biomarkers 2
NCT04912609	Not specified	COMPLETED	Trehalose Administration in Subjects With Spastic Paraplegia 11 (3AL-SPG11)