FEZF1

Summary

FEZF1 (FEZ family zinc finger 1, HGNC:22788) is a protein-coding gene on chromosome 7q31.32, encoding Fez family zinc finger protein 1 (A0PJY2). Transcription repressor.

This gene encodes a transcriptional repressor that belongs to the zinc finger double domain protein family. The encoded protein is thought to play a role in the embryonic migration of gonadotropin-releasing hormone neurons into the brain. Mutations in this gene are associated with hypogonadotropic hypogonadism-22 with anosmia. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 389549 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypogonadotropic hypogonadism 22 with or without anosmia (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 5
• Clinical variants (ClinVar): 137 total — 3 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 57
• Transcription factor: yes — 10 downstream targets (CollecTRI)
• MANE Select transcript: NM_001024613

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22788
Approved symbol	FEZF1
Name	FEZ family zinc finger 1
Location	7q31.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000128610
Ensembl biotype	protein_coding
OMIM	613301
Entrez	389549

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000418046, ENST00000427185, ENST00000442488, ENST00000914446, ENST00000914447, ENST00000914448, ENST00000914449, ENST00000914450, ENST00000914451, ENST00000914452

RefSeq mRNA: 2 — MANE Select: NM_001024613 NM_001024613, NM_001160264

CCDS: CCDS34741, CCDS55157

Canonical transcript exons

ENST00000442488 — 4 exons

Exon	Start	End
ENSE00000882010	122301303	122302355
ENSE00000882011	122303177	122303311
ENSE00001595254	122303637	122304750
ENSE00002333095	122302799	122302931

Expression profiles

Bgee: expression breadth broad, 52 present calls, max score 79.41.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.6359 / max 200.8135, expressed in 148 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
85930	0.7291	102
85928	0.4616	59
85933	0.1330	55
85934	0.1099	43
85926	0.0730	34
85929	0.0638	34
85935	0.0333	22
85927	0.0323	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.41	silver quality
hypothalamus	UBERON:0001898	71.73	gold quality
caudate nucleus	UBERON:0001873	70.05	gold quality
amygdala	UBERON:0001876	68.76	gold quality
temporal lobe	UBERON:0001871	68.66	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	68.14	gold quality
putamen	UBERON:0001874	67.56	gold quality
left testis	UBERON:0004533	66.23	gold quality
testis	UBERON:0000473	66.20	gold quality
nucleus accumbens	UBERON:0001882	64.82	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	64.06	gold quality
right testis	UBERON:0004534	63.97	gold quality
substantia nigra	UBERON:0002038	59.58	gold quality
adenohypophysis	UBERON:0002196	50.53	gold quality
brain	UBERON:0000955	48.66	gold quality
primary visual cortex	UBERON:0002436	47.73	gold quality
cortical plate	UBERON:0005343	44.63	gold quality
pituitary gland	UBERON:0000007	43.82	gold quality
bone marrow cell	CL:0002092	42.42	gold quality
Brodmann (1909) area 9	UBERON:0013540	41.50	gold quality
ventricular zone	UBERON:0003053	40.82	gold quality
Ammon’s horn	UBERON:0001954	39.64	gold quality
heart left ventricle	UBERON:0002084	39.62	gold quality
prefrontal cortex	UBERON:0000451	38.63	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	38.63	silver quality
dorsolateral prefrontal cortex	UBERON:0009834	38.62	gold quality
cerebral cortex	UBERON:0000956	38.43	gold quality
apex of heart	UBERON:0002098	38.15	silver quality
calcaneal tendon	UBERON:0003701	37.92	silver quality
frontal cortex	UBERON:0001870	37.83	silver quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6524	yes	138.16
E-GEOD-93593	yes	13.83
E-ANND-3	no	1.80

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

10 targets.

Target	Regulation
FEZF1
HES5	Repression
KRAS	Unknown
NANOG	Repression
NEUROG2	Activation
OTX2	Activation
PAX6	Activation
POU5F1	Repression
SOX2	Activation
VGLL2

Upstream regulators (CollecTRI, top): FEZF1, FOXC1, NEUROG2, SP1

miRNA regulators (miRDB)

45 targeting FEZF1, 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-8485	100.00	77.57	4731
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-4696	99.48	67.48	1040

Literature-anchored findings (GeneRIF, showing 14)

• Study is the first to report that ZNF312b, a novel transcription factor, was associated with tumorigenicity of gastric cancer. (PMID:19318583)
• the aberrant expression of ZNF312b promotes gastric tumorigenesis through epigenetic modification of its promoter region and provides a molecular mechanism for ZNF312b expression to contribute to the progression of gastric cancer. (PMID:21170990)
• Fezf1 and Fezf2 accomplish both independent and redundant functions across diverse tissue and cell types. [Review] (PMID:24913420)
• Mutations in FEZF1 cause Kallmann syndrome. (PMID:25192046)
• SEZ6L, HISPPD1, FEZF1, SAMD11 gene variants may be associated with autism spectrum disorder. (PMID:26204995)
• High expression of long noncoding RNA FEZF1 was significantly associated with later stage and higher grade of gastric cancer. (PMID:29239821)
• loss of FEZF1 impairs the pluripotency exit of hESCs during neural specification, which partially explains the neural induction defect caused by FEZF1 deletion. (PMID:29318501)
• provides clinical evidence that FEZF1-AS1 may be a possible biomarker of poor prognosis in Cervical Cancer. (PMID:29917186)
• FEZF1 was significantly increased in glioma tissues. Over-expressed FIZF1 was associated with reduced survival. (PMID:30030762)
• FEZF1-AS1 regulated activation of JAK-STAT3 signaling pathway by modulating STAT3 phosphorylation. Knockdown of FEZF1-AS1 significantly impaired the phosphorylation of STAT3. Study demonstrated that FEZF1-AS1 exerted an oncogenic role in ovarian cancer via modulating JAK-STAT3 pathway. (PMID:30416194)
• Mechanism of lncRNA FEZF1-AS1 in promoting the occurrence and development of oral squamous cell carcinoma through targeting miR-196a. (PMID:31378890)
• Circulatinglong non-coding RNA FEZF1-AS1 and AFAP1-AS1 serve as potential diagnostic biomarkers for gastric cancer. (PMID:31785996)
• Long Non-coding RNA FEZF1-AS1 Promotes Growth and Reduces Apoptosis Through Regulation of miR-363-3p/PAX6 Axis in Retinoblastoma. (PMID:33432525)
• LncRNA FEZF1-AS1 promotes colorectal cancer progression through regulating the miR-363-3p/PRRX1 pathway. (PMID:34286520)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fezf1	ENSDARG00000010270
mus_musculus	Fezf1	ENSMUSG00000029697
rattus_norvegicus	Fezf1	ENSRNOG00000007608

Paralogs (28): ZNF280C (ENSG00000056277), ZBTB25 (ENSG00000089775), PRDM13 (ENSG00000112238), BCL6 (ENSG00000113916), ZBTB46 (ENSG00000130584), PRDM12 (ENSG00000130711), ZNF280D (ENSG00000137871), NACC2 (ENSG00000148411), FEZF2 (ENSG00000153266), ZBTB7B (ENSG00000160685), NACC1 (ENSG00000160877), BCL6B (ENSG00000161940), GFI1 (ENSG00000162676), GFI1B (ENSG00000165702), ZBTB49 (ENSG00000168826), ZNF280A (ENSG00000169548), ZNF581 (ENSG00000171425), ZNF524 (ENSG00000171443), ZBTB26 (ENSG00000171448), ZBTB21 (ENSG00000173276), ZNF683 (ENSG00000176083), ZBTB33 (ENSG00000177485), ZBTB3 (ENSG00000185670), ZBTB6 (ENSG00000186130), ZBTB14 (ENSG00000198081), ZBTB12 (ENSG00000204366), ZNF580 (ENSG00000213015), ZNF280B (ENSG00000275004)

Protein

Protein identifiers

Fez family zinc finger protein 1 — A0PJY2 (reviewed: A0PJY2)

Alternative names: Zinc finger protein 312B

All UniProt accessions (2): A0PJY2, C9J0C5

UniProt curated annotations — full annotation on UniProt →

Function. Transcription repressor. Involved in the axonal projection and proper termination of olfactory sensory neurons (OSN). Plays a role in rostro-caudal patterning of the diencephalon and in prethalamic formation. Expression is required in OSN to cell-autonomously regulate OSN axon projections. Regulates non-cell-autonomously the layer formation of the olfactory bulb development and the interneurons. May be required for correct rostral migration of the interneuron progenitors.

Subcellular location. Nucleus.

Tissue specificity. Expressed in brain. Little or no expression in other tissues. Overexpressed specifically in gastric cancers. A 2- to 20-fold increase is found in over 50% of gastric cancer tissues.

Disease relevance. Hypogonadotropic hypogonadism 22 with or without anosmia (HH22) [MIM:616030] A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Triggers oncogenic activity specifically in gastric tumors through activation of KRAS in the ERK signaling pathway.

Similarity. Belongs to the krueppel C2H2-type zinc-finger protein family.

Isoforms (3)

UniProt ID	Names	Canonical?
A0PJY2-1	1	yes
A0PJY2-2	2
A0PJY2-3	3

RefSeq proteins (2): NP_001019784, NP_001153736 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096, PF13912

UniProt features (13 total): zinc finger region 6, splice variant 2, chain 1, sequence variant 1, region of interest 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A0PJY2-F1	56.91	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 180 (showing top): GOBP_POSITIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_FOREBRAIN_REGIONALIZATION, GOBP_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_ANTERIOR_POSTERIOR_PATTERN_SPECIFICATION, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, GOBP_NEURON_MIGRATION, GOBP_HEAD_DEVELOPMENT, GOBP_OLFACTORY_LOBE_DEVELOPMENT, TANAKA_METHYLATED_IN_ESOPHAGEAL_CARCINOMA, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, GOBP_TELENCEPHALON_DEVELOPMENT

GO Biological Process (17): regulation of transcription by RNA polymerase II (GO:0006357), axon guidance (GO:0007411), negative regulation of cell population proliferation (GO:0008285), olfactory bulb development (GO:0021772), forebrain anterior/posterior pattern specification (GO:0021797), central nervous system neuron differentiation (GO:0021953), cell dedifferentiation (GO:0043697), positive regulation of neuron differentiation (GO:0045666), positive regulation of DNA-templated transcription (GO:0045893), regulation of neurogenesis (GO:0050767), interneuron migration (GO:1904936), negative regulation of transcription by RNA polymerase II (GO:0000122), nervous system development (GO:0007399), telencephalon development (GO:0021537), cell differentiation (GO:0030154), neuron differentiation (GO:0030182), forebrain development (GO:0030900)

GO Molecular Function (9): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), transcription cis-regulatory region binding (GO:0000976), DNA binding (GO:0003677), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleoplasm (GO:0005654), cytosol (GO:0005829), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	3
anatomical structure development	3
transcription by RNA polymerase II	2
neuron differentiation	2
cellular developmental process	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
cellular anatomical structure	2
axonogenesis	1
neuron projection guidance	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
olfactory lobe development	1
anterior/posterior pattern specification	1
forebrain regionalization	1
central nervous system development	1
dedifferentiation	1
positive regulation of cell differentiation	1
regulation of neuron differentiation	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
neurogenesis	1
regulation of nervous system development	1
regulation of cell development	1
neuron migration	1
regulation of transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
system development	1
forebrain development	1
cell differentiation	1
generation of neurons	1
brain development	1
cis-regulatory region sequence-specific DNA binding	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
transition metal ion binding	1
transcription regulatory region nucleic acid binding	1

Protein interactions and networks

STRING

890 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FEZF1	PROKR2	Q8NFJ6	598
FEZF1	HS6ST1	O60243	583
FEZF1	ANOS1	P23352	561
FEZF1	KRAS	P01116	556
FEZF1	NSMF	Q6X4W1	556
FEZF1	PROK2	Q9HC23	548
FEZF1	TACR3	P29371	511
FEZF1	LHX5	Q9H2C1	503
FEZF1	IL17RD	Q8NFM7	486
FEZF1	TAC3	Q9UHF0	480
FEZF1	FLRT3	Q9NZU0	476
FEZF1	FES	P07332	475
FEZF1	ZNF385B	Q569K4	459
FEZF1	CHD7	Q9P2D1	452
FEZF1	GNRHR	P30968	450

IntAct

21 interactions, top by confidence:

A	B	Type	Score
FEZF1	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.560
FEZF1	CYSRT1	psi-mi:“MI:0915”(physical association)	0.560
FEZF1	KRTAP1-1	psi-mi:“MI:0915”(physical association)	0.560
FEZF1	MDFI	psi-mi:“MI:0915”(physical association)	0.560
FEZF1	KRT40	psi-mi:“MI:0915”(physical association)	0.560
FEZF1	FHL5	psi-mi:“MI:0915”(physical association)	0.560
CAMKK2	FEZF1	psi-mi:“MI:0914”(association)	0.350
FEZF1	ZZEF1	psi-mi:“MI:0914”(association)	0.350
FEZF1	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.000
FEZF1	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
FEZF1	KRTAP1-1	psi-mi:“MI:0915”(physical association)	0.000
FEZF1	KRT40	psi-mi:“MI:0915”(physical association)	0.000
FEZF1	MDFI	psi-mi:“MI:0915”(physical association)	0.000
FEZF1	FHL5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (28): FEZF1 (Two-hybrid), FEZF1 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP1-1 (Two-hybrid), CYSRT1 (Two-hybrid), KRT40 (Two-hybrid), IFT74 (Affinity Capture-MS), CENPB (Affinity Capture-MS), MTMR4 (Affinity Capture-MS), NEURL4 (Affinity Capture-MS), LRP1B (Affinity Capture-MS), HERC2 (Affinity Capture-MS), ZZEF1 (Affinity Capture-MS), C18orf25 (Affinity Capture-MS), TLE4 (Affinity Capture-MS)

ESM2 similar proteins: A0JPB4, A0PJY2, B0K011, O08876, O15090, O57415, O62651, O70237, O75626, O95863, P19544, P22561, P41183, P49952, P55878, P86413, Q02085, Q08DS3, Q0IHB8, Q0P4W9, Q0VDQ9, Q25C93, Q28G88, Q2TAR3, Q2VWH6, Q32NK7, Q3MHQ4, Q3T135, Q3UH06, Q567J8, Q5T0B9, Q5VTD9, Q5XJQ7, Q60636, Q62255, Q66JF8, Q6AY34, Q6DBW0, Q6NRM0, Q804Q5

Diamond homologs: A0PJY2, Q0P4W9, Q0VDQ9, Q25C93, Q28G88, Q2TAR3, Q2VWH6, Q804Q5, Q8TBJ5, Q9ESP5, Q9IAJ2, Q9VQ56, P60319

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	74
Likely benign	32
Benign	21

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
156219	NM_001024613.4(FEZF1):c.832C>T (p.His278Tyr)	Pathogenic
156220	NM_001024613.4(FEZF1):c.653del (p.Phe218fs)	Pathogenic
1703560	Single allele	Pathogenic
1687716	Single allele	Likely pathogenic

SpliceAI

343 predictions. Top by Δscore:

Variant	Effect	Δscore
7:122302351:ATTCC:A	acceptor_gain	1.0000
7:122302352:TTCC:T	acceptor_gain	1.0000
7:122302353:TCC:T	acceptor_gain	1.0000
7:122302354:CC:C	acceptor_gain	1.0000
7:122302354:CCC:C	acceptor_gain	1.0000
7:122302355:CC:C	acceptor_gain	1.0000
7:122302355:CCT:C	acceptor_loss	1.0000
7:122302356:C:CC	acceptor_gain	1.0000
7:122302794:CATA:C	donor_loss	1.0000
7:122302795:ATAC:A	donor_loss	1.0000
7:122302798:CCTT:C	donor_loss	1.0000
7:122302927:TTTTC:T	acceptor_gain	1.0000
7:122302928:TTTC:T	acceptor_gain	1.0000
7:122302929:TTC:T	acceptor_gain	1.0000
7:122302930:TC:T	acceptor_gain	1.0000
7:122302930:TCCTA:T	acceptor_loss	1.0000
7:122302931:CC:C	acceptor_gain	1.0000
7:122302931:CCTA:C	acceptor_loss	1.0000
7:122302932:C:CA	acceptor_loss	1.0000
7:122302932:C:CC	acceptor_gain	1.0000
7:122302933:T:A	acceptor_loss	1.0000
7:122302937:C:CT	acceptor_gain	1.0000
7:122302938:A:T	acceptor_gain	1.0000
7:122302362:C:CT	acceptor_gain	0.9800
7:122303218:G:A	donor_gain	0.9800
7:122303631:ACTT:A	donor_loss	0.9800
7:122303632:CT:C	donor_loss	0.9800
7:122303633:TTGC:T	donor_loss	0.9800
7:122303636:C:A	donor_loss	0.9800
7:122303650:T:TA	donor_gain	0.9700

AlphaMissense

3131 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:122302171:A:C	H418Q	1.000
7:122302171:A:T	H418Q	1.000
7:122302173:G:C	H418D	1.000
7:122302181:A:G	L415P	1.000
7:122302193:C:A	R411M	1.000
7:122302198:G:C	F409L	1.000
7:122302198:G:T	F409L	1.000
7:122302199:A:G	F409S	1.000
7:122302200:A:G	F409L	1.000
7:122302210:G:C	C405W	1.000
7:122302211:C:T	C405Y	1.000
7:122302212:A:G	C405R	1.000
7:122302219:G:C	C402W	1.000
7:122302220:C:G	C402S	1.000
7:122302221:A:G	C402R	1.000
7:122302221:A:T	C402S	1.000
7:122302225:G:C	F400L	1.000
7:122302225:G:T	F400L	1.000
7:122302227:A:G	F400L	1.000
7:122302255:G:C	H390Q	1.000
7:122302255:G:T	H390Q	1.000
7:122302257:G:C	H390D	1.000
7:122302257:G:T	H390N	1.000
7:122302265:A:G	L387P	1.000
7:122302282:G:C	F381L	1.000
7:122302282:G:T	F381L	1.000
7:122302284:A:G	F381L	1.000
7:122302294:G:C	C377W	1.000
7:122302295:C:G	C377S	1.000
7:122302295:C:T	C377Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000106128 (7:122304145 G>C), RS1000193580 (7:122307152 C>A), RS1001070986 (7:122301864 G>A,T), RS1001440074 (7:122301539 A>G), RS1001484114 (7:122306304 T>C,G), RS1001493630 (7:122306555 G>T), RS1001724202 (7:122312131 G>A,T), RS1001821028 (7:122305047 C>G), RS1001830894 (7:122305392 G>A), RS1001873752 (7:122310743 C>G,T), RS1002008838 (7:122310668 G>T), RS1002809864 (7:122311808 A>G), RS1003025951 (7:122309069 G>A), RS1003483720 (7:122304795 T>C,G), RS1003730796 (7:122309580 A>G)

Disease associations

OMIM: gene MIM:613301 | disease phenotypes: MIM:146110, MIM:616030

GenCC curated gene-disease

Disease	Classification	Inheritance
hypogonadotropic hypogonadism 22 with or without anosmia	Strong	Autosomal recessive
Kallmann syndrome	Supportive	Autosomal dominant

Mondo (5): hypogonadotropic hypogonadism 7 with or without anosmia (MONDO:0007794), hypogonadotropic hypogonadism 22 with or without anosmia (MONDO:0014461), amenorrhea (MONDO:0001836), ring chromosome 7 (MONDO:0015441), Kallmann syndrome (MONDO:0018800)

Orphanet (3): Normosmic congenital hypogonadotropic hypogonadism (Orphanet:432), Kallmann syndrome (Orphanet:478), Ring chromosome 7 syndrome (Orphanet:1449)

HPO phenotypes

57 total (30 of 57 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000008	Abnormal morphology of female internal genitalia
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000054	Micropenis
HP:0000104	Renal agenesis
HP:0000135	Hypogonadism
HP:0000144	Decreased fertility
HP:0000175	Cleft palate
HP:0000407	Sensorineural hearing impairment
HP:0000458	Anosmia
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000551	Color vision defect
HP:0000639	Nystagmus
HP:0000771	Gynecomastia
HP:0000786	Primary amenorrhea
HP:0000789	Infertility
HP:0000823	Delayed puberty
HP:0000830	Anterior hypopituitarism
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001260	Dysarthria
HP:0001288	Gait disturbance
HP:0001324	Muscle weakness
HP:0001335	Bimanual synkinesia
HP:0001337	Tremor
HP:0001513	Obesity
HP:0001608	Abnormality of the voice

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST007576_193	Chronotype	3.000000e-10
GCST010135_9	Oily fish consumption	8.000000e-12
GCST010140_1	Pork consumption	8.000000e-12
GCST010291_2	Attention deficit hyperactivity disorder	2.000000e-08
GCST012490_380	Femur bone mineral density x serum urate levels interaction	4.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement
EFO:0008111	diet measurement
EFO:0004531	urate measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D000568	Amenorrhea	C23.550.568.500
D017436	Kallmann Syndrome	C12.050.351.875.253.096.750; C12.200.706.316.096.750; C12.800.316.096.750; C16.131.939.316.096.750; C16.320.467; C19.391.119.096.750; C19.391.482.600
C537813	Chromosome 7 ring syndrome (supp.)
C562785	Idiopathic Hypogonadotropic Hypogonadism (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
ethyl-p-hydroxybenzoate	decreases expression	1
arsenite	increases methylation	1
ferrous chloride	decreases expression	1
bisphenol S	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Okadaic Acid	increases expression	1
Acrylamide	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_XV64	HEK293 eGFP-FEZF1	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01403532	PHASE4	COMPLETED	Sequential Therapy for Hypogonadotropic Hypogonadism
NCT02880280	PHASE4	UNKNOWN	Human Menopausal Gonadotropin Combining With Human Chorionic Gonadotropin Treat Congenital Hypogonadotropic Hypogonadism
NCT03687606	PHASE4	UNKNOWN	Efficacy and Safety of Long Term Use of hCG or hCG Plus hMG in Males With Isolated Hypogonadotropic Hypogonadism (IHH)
NCT01103518	PHASE4	UNKNOWN	Ethinyl Estradiol and Cyproterone Acetate in Irregular Menstruation
NCT01206153	PHASE4	COMPLETED	Metformin for Treatment Antipsychotic Induced Amenorrhea in Female Schizophrenic Patients
NCT02393482	PHASE4	UNKNOWN	Psychological Impact of Amenorrhea in Women With Endometriosis
NCT00827151	PHASE3	WITHDRAWN	Bone Mass Accrual in Adolescent Athletes
NCT00064987	PHASE2	TERMINATED	Follicle Stimulating Hormone (FSH) to Improve Testicular Development in Men With Hypogonadism
NCT00130117	PHASE2	COMPLETED	Study of Leptin for the Treatment of Hypothalamic Amenorrhea
NCT00152282	PHASE2	COMPLETED	A Study to Evaluate the Safety and Effectiveness of Asoprisnil and Estrogen Administration to Postmenopausal Women
NCT00196391	PHASE2	COMPLETED	A Trial to Evaluate DR-2021 in Women With Secondary Amenorrhea
NCT00383656	PHASE2	UNKNOWN	Pulsatile GnRH in Anovulatory Infertility
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT00392756	PHASE1	COMPLETED	Examination of Idiopathic Hypogonadotropic Hypogonadism (IHH)and Kallmann Syndrome (KS)
NCT00493961	PHASE1	COMPLETED	Studying the Effects of 7 Days of Gonadotropin Releasing Hormone (GnRH) Treatment in Men With Hypogonadism
NCT00914823	PHASE1	COMPLETED	Kisspeptin Administration in the Adult
NCT01438034	PHASE1	COMPLETED	Kisspeptin in the Evaluation of Delayed Puberty
NCT03118479	PHASE1	TERMINATED	Effect of Varying Testosterone Levels on Insulin Sensitivity in Men With Idiopathic Hypogonadotropic Hypogonadism (IHH)
NCT00881608	PHASE1	TERMINATED	Study to Evaluate Menses Induction in Women Administered Proellex
NCT07152730	PHASE1	WITHDRAWN	A Study to Measure Pharmacokinetic (PK) Concentrations of Gonadotropin-Releasing Hormone Delivered by the OmniPod Pump
NCT00392457	Not specified	COMPLETED	Investigating the Regulation of Reproductive Hormones in Adult Men
NCT00494169	Not specified	COMPLETED	Investigation of the Genetic Causes of Kallmann Syndrome and Reproductive Disorders
NCT00623116	Not specified	UNKNOWN	A Study to Characterize Epidemiology, Clinical and Genetic Features of Kallmann Syndrome in Finland
NCT01601171	Not specified	RECRUITING	Genetics of Reproductive Disorders (Including Kallmann Syndrome) and Cleft Lip and/or Palate
NCT01914172	Not specified	COMPLETED	Health Needs of Patients With Kallmann Syndrome
NCT04463316	Not specified	RECRUITING	GROWing Up With Rare GENEtic Syndromes
NCT04733274	Not specified	ACTIVE_NOT_RECRUITING	Patient and Healthcare Professional Views on Genetic/Genomic Information and Testing
NCT05971836	Not specified	ACTIVE_NOT_RECRUITING	The Molecular Basis of Inherited Reproductive Disorders
NCT03916978	PHASE2/PHASE3	RECRUITING	Autologous PRP Intra Ovarian Infusion to Restore Ovarian Function in Menopausal Women
NCT00556400	PHASE1/PHASE2	TERMINATED	Treatment of Menorrhagia in Women With Thrombocytopenia Using Platelets or Platelets and Hormones
NCT01187043	PHASE1/PHASE2	COMPLETED	Determination of the Lowest, Safe and Effective Dose of Proellex
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00011388	Not specified	COMPLETED	Reproductive Effects of Pesticide, PCB and Mercury Exposure in Laotian Immigrants
NCT00243607	Not specified	COMPLETED	Hydrotherapy Against Menopausal Symptoms in Breast Cancer Survivors
NCT00260286	Not specified	COMPLETED	Effects of Gynecological Age on LH Sensitivity to Energy Availability
NCT00456274	Not specified	UNKNOWN	Baselines in Reproductive Disorders
NCT00589654	Not specified	ACTIVE_NOT_RECRUITING	Menstrual Cycle Maintenance and Quality of Life: A Prospective Study
NCT01423487	Not specified	WITHDRAWN	Efficacy and Safety of Metformin in Preventing Patients With Risperidone From Weight Gain and Amenorrhea
NCT01500447	Not specified	RECRUITING	Inherited Reproductive Disorders
NCT01511588	Not specified	COMPLETED	Hormonal Regulation of Puberty and Fertility