MNX1

Summary

MNX1 (motor neuron and pancreas homeobox 1, HGNC:4979) is a protein-coding gene on chromosome 7q36.3, encoding Motor neuron and pancreas homeobox protein 1 (P50219). Transcription factor. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a nuclear protein, which contains a homeobox domain and is a transcription factor. Mutations in this gene result in Currarino syndrome, an autosomic dominant congenital malformation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 3110 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Currarino triad (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 7
• Clinical variants (ClinVar): 423 total — 32 pathogenic, 13 likely-pathogenic
• Phenotypes (HPO): 42
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_005515

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4979
Approved symbol	MNX1
Name	motor neuron and pancreas homeobox 1
Location	7q36.3
Locus type	gene with protein product
Status	Approved
Aliases	HB9, HOXHB9, SCRA1
Ensembl gene	ENSG00000130675
Ensembl biotype	protein_coding
OMIM	142994
Entrez	3110

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000252971, ENST00000425745, ENST00000428439, ENST00000469500, ENST00000474448, ENST00000479817, ENST00000543409, ENST00000605400

RefSeq mRNA: 2 — MANE Select: NM_005515 NM_001165255, NM_005515

CCDS: CCDS34788, CCDS55187

Canonical transcript exons

ENST00000252971 — 3 exons

Exon	Start	End
ENSE00001381525	157009660	157010663
ENSE00003464207	157006479	157006639
ENSE00003850769	157004854	157005873

Expression profiles

Bgee: expression breadth ubiquitous, 130 present calls, max score 90.87.

FANTOM5 (CAGE): breadth broad, TPM avg 1.7720 / max 135.6982, expressed in 329 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
87063	1.6518	325
87062	0.1202	71

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	90.87	silver quality
body of pancreas	UBERON:0001150	88.79	gold quality
pancreas	UBERON:0001264	83.97	gold quality
endometrium epithelium	UBERON:0004811	83.72	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.61	gold quality
mucosa of transverse colon	UBERON:0004991	82.23	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.70	silver quality
type B pancreatic cell	CL:0000169	81.68	silver quality
colonic mucosa	UBERON:0000317	79.96	gold quality
mucosa of sigmoid colon	UBERON:0004993	79.36	silver quality
duodenum	UBERON:0002114	77.73	gold quality
jejunal mucosa	UBERON:0000399	77.06	silver quality
islet of Langerhans	UBERON:0000006	76.46	gold quality
rectum	UBERON:0001052	73.40	gold quality
ileal mucosa	UBERON:0000331	72.12	gold quality
secondary oocyte	CL:0000655	71.49	gold quality
buccal mucosa cell	CL:0002336	71.04	gold quality
small intestine	UBERON:0002108	71.03	gold quality
small intestine Peyer’s patch	UBERON:0003454	70.71	gold quality
transverse colon	UBERON:0001157	70.29	gold quality
esophagus squamous epithelium	UBERON:0006920	69.56	gold quality
epithelium of esophagus	UBERON:0001976	67.13	gold quality
male germ cell	CL:0000015	66.67	silver quality
sperm	CL:0000019	66.60	silver quality
superficial temporal artery	UBERON:0001614	66.59	gold quality
jejunum	UBERON:0002115	65.42	silver quality
pituitary gland	UBERON:0000007	64.70	gold quality
body of stomach	UBERON:0001161	64.06	gold quality
intestine	UBERON:0000160	63.62	gold quality
olfactory bulb	UBERON:0002264	63.59	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.26
E-HCAD-13	no	3.08

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

6 targets.

Target	Regulation
IL6
INS
MEN1
MNX1
PIK3R1
PTGER2

JASPAR motifs

Motif	Name	Family
MA0707.1	MNX1	HOX
MA0707.2	MNX1	HOX
MA0707.3	MNX1	HOX

JASPAR matrix evidence (PMIDs): PMID:18585360

Upstream regulators (CollecTRI, top): MNX1, MYC

miRNA regulators (miRDB)

35 targeting MNX1, 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-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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-410-3P	99.27	69.98	2457

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• mutation in the HLXB9 transcription factor causes an autosomal dominant form of sacral agenesis (PMID:11940082)
• The chromosomal rearrangements of the HLXB9 protein locus at 7q36 were not detected in Hodgkin lymphoma cells unlike acute myeloid leukemia subsets expressing HLXB9. (PMID:15772702)
• High incidence of t(7;12)(q36;p13) in infant myeloid leukemia is associated with ectopic expression of HLXB9. (PMID:16646086)
• This study confirms that familial Currarino syndrome (CS) patients in Korea have the same genetic background as other ethnicities and reaffirms the phenotype variability among CS patients with the same mutation. (PMID:17612791)
• report 23 novel mutations in 26 patients among a series of 50 index cases with Currarino syndrome (PMID:18449898)
• MNX1-ETV6 fusion gene in an acute megakaryoblastic leukemia. (PMID:18940475)
• Ectopic expression of the HLXB9 gene is associated with an altered nuclear position in t(7;12) leukaemias (PMID:19212340)
• HLXB9 is overexpressed in patients with infantile acute myeloid leukemia. (PMID:19446746)
• study reports on the MNX1 mutations in a family segregating Currarino syndrome (CS) & 3 sporadic CS patients & on clinical characteristics of the affected individuals (PMID:19853743)
• Incomeplete Curarino syndrome with more advantageous prognosis with autosomal domiant pattern homebox gene HLXBV9 mutation. (PMID:20146075)
• Hypermethylation of HLXB9 results in loss of expression and is associated with acute lymphoblastic leukemia. (PMID:21069786)
• 2 previously described mutations, 1 de novo nonsense mutation (p.Gln212X) & 1 maternally inherited frameshift mutation (p.Pro18ProfsX38)were found among 14 Currarino syndrome patients with presacral tumors. (PMID:21763840)
• a new HLXB9 gene mutation identified in a Chinese family with members suffering from Currarino syndrome (PMID:21960426)
• two novel mutations in the MNX1 gene in cases with Currarino syndrome (PMID:22820079)
• HB9 binds to the prostaglandin E receptor 2 promoter and inhibits intracellular cAMP mobilization in leukemic cells. (PMID:23048027)
• study describes a Norwegian family with typical Currarino syndrome in which a heterozygous deletion removes the entire MNX1 gene but no other known genes; also report MNX1 mutations in 3other Norwegian families and confirm that the GCC12 repeat (c.373_375[12]) is a normal allelic variant (PMID:23370340)
• study reports the results of MNX1 mutational screening in a series of 28 cases suspected having Currarino Syndrome and characterization of 10 novel mutations (PMID:24095820)
• NKX2-2 and MNX1 are etiological genes for neonatal diabetes. (PMID:24411943)
• Both pHLXB9 and active GSK-3beta are elevated in beta cells with menin knockdown, in MEN1-associated beta cell tumors (insulinomas) (PMID:24425879)
• The nuclear positioning of the HLXB9 gene was monitored at different stages. (PMID:25136833)
• The results illustrated miR-200a and miR-141 could inhibit the expression of Hlxb9 by binding to its mRNA 3’UTR. Furthermore, the expression of miR-200a and miR-141 was almost reciprocal to that of Hlxb9. Overexpression of miR-200a and miR-141 downregulated the expression of pancreatic progenitor cell markers Hlxb9 (PMID:26801823)
• MNX1 as a novel targetable oncogene increased in African-American (AA) prostate cancer that is associated with aggressive disease. (PMID:27578002)
• Findings demonstrated for the first time that lncRNA MNX1-AS1 functions as an oncogene in ovarian cancer. (PMID:28414551)
• Findings identify RGS12 as a candidate tumor-suppressor gene in AA prostate cancer, which acts by decreasing expression of AKT and MNX1, establishing a novel oncogenic axis in this disparate disease setting. (PMID:28611045)
• Pathogenic variants in MNX1 were detected in 28% of all CS cases and 25% of sporadic cases. The clinical phenotype was variable in patients with and without pathogenic variants; no significant genotype-phenotype correlation was observed. (PMID:29401559)
• MNX1-AS1 promoted the proliferation, migration, and invasion of GBM cells through inhibiting miR-4443. (PMID:29678219)
• MNX1 may directly regulate TrkB expression, which may increase their metastatic potential via suppression of anoikis and enhanced adhesion to the ECM. (PMID:30066929)
• the novel findings of HB9-dependent premature senescence and myeloid-biased perturbed hematopoietic differentiation, for the first time shed light on the oncogenic properties of HB9 in translocation t(7;12) acute myeloid leukemia. (PMID:30093397)
• Study showed that ectopic expression of MNX1 activates the Wnt/beta-catenin signaling and upregulates the expression of c-Myc and CCND1, the downstream genes of Wnt/beta-catenin signaling. MNX1 plays an indispensable role in promoting of human CRC progression. (PMID:30614606)
• MNX1-AS1 long noncoding RNA upregulation may have a role in gastric cancer and predicts its prognosis (PMID:30821221)
• The overexpression of MNX1 promoted cervical cancer cells proliferation, migration, and invasion. (PMID:31436258)
• MNX1-AS1 accelerates the epithelial-mesenchymal transition in osteosarcoma cells by activating MNX1 as a functional oncogene. (PMID:31646549)
• Novel MNX1 mutations and genotype-phenotype analysis of patients with Currarino syndrome. (PMID:32571425)
• Long noncoding RNA MNX1-AS1 functions as a competing endogenous RNA to regulate epithelial-mesenchymal transition by sponging MiR-744-5p in colorectal cancer. (PMID:33590038)
• Global transcriptome profile of the developmental principles of in vitro iPSC-to-motor neuron differentiation. (PMID:33602141)
• Presacral neuroendocrine tumors associated with the Currarino syndrome. (PMID:33650152)
• MNX1-HNF1B Axis Is Indispensable for Intraductal Papillary Mucinous Neoplasm Lineages. (PMID:34953915)
• An induced pluripotent stem cell t(7;12)(q36;p13) acute myeloid leukemia model shows high expression of MNX1 and a block in differentiation of the erythroid and megakaryocytic lineages. (PMID:35583991)
• Pan-Cancer Analysis Identifies MNX1 and Associated Antisense Transcripts as Biomarkers for Cancer. (PMID:36429006)
• Aberrant MNX1 expression associated with t(7;12)(q36;p13) pediatric acute myeloid leukemia induces the disease through altering histone methylation. (PMID:37317878)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mnx1	ENSDARG00000035984
mus_musculus	Mnx1	ENSMUSG00000001566
rattus_norvegicus	Mnx1	ENSRNOG00000046959

Protein

Protein identifiers

Motor neuron and pancreas homeobox protein 1 — P50219 (reviewed: P50219)

Alternative names: Homeobox protein HB9

All UniProt accessions (6): P50219, C9JFT4, C9K088, S4R364, S4R3G1, S4R464

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor. Recognizes and binds to the regulatory elements of target genes, such as visual system homeobox CHX10, negatively modulating transcription. Plays a role in establishing motor neuron identity, in concert with LIM domain transcription factor LMO4. Involved in negatively modulating transcription of interneuron genes in motor neurons, acting, at least in part, by blocking regulatory sequence interactions of the ISL1-LHX3 complex. Involved in pancreas development and function; may play a role in pancreatic cell fate specification.

Subcellular location. Nucleus.

Tissue specificity. Expressed in lymphoid and pancreatic tissues.

Disease relevance. Currarino syndrome (CURRAS) [MIM:176450] The triad of a presacral tumor, sacral agenesis and anorectal malformation constitutes the Currarino syndrome which is caused by dorsal-ventral patterning defects during embryonic development. The syndrome occurs in the majority of patients as an autosomal dominant trait. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
P50219-1	1	yes
P50219-2	2

RefSeq proteins (2): NP_001158727, NP_005506* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR020479	HD_metazoa	Domain
IPR042768	MNX1/Ceh-12	Family

Pfam: PF00046

UniProt features (34 total): sequence variant 11, compositionally biased region 7, sequence conflict 6, modified residue 3, region of interest 3, splice variant 2, chain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P50219-F1	59.46	0.16

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): 1, 77, 79

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 200 (showing top): GOBP_SPINAL_CORD_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, FISCHER_G1_S_CELL_CYCLE, GOBP_NEUROGENESIS, GOBP_CELL_DIFFERENTIATION_IN_SPINAL_CORD, GOBP_SPINAL_CORD_MOTOR_NEURON_DIFFERENTIATION, GOBP_PANCREAS_DEVELOPMENT, GOBP_VENTRAL_SPINAL_CORD_DEVELOPMENT, GOBP_SPINAL_CORD_MOTOR_NEURON_CELL_FATE_SPECIFICATION, GOBP_ENDOCRINE_PANCREAS_DEVELOPMENT, GOBP_NEURON_FATE_SPECIFICATION, GOBP_CENTRAL_NERVOUS_SYSTEM_NEURON_DIFFERENTIATION, SHIN_B_CELL_LYMPHOMA_CLUSTER_1, GOBP_ENDOCRINE_SYSTEM_DEVELOPMENT, GOBP_CELL_PROJECTION_ORGANIZATION

GO Biological Process (6): central nervous system development (GO:0007417), spinal cord motor neuron cell fate specification (GO:0021520), endocrine pancreas development (GO:0031018), neuron projection morphogenesis (GO:0048812), negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (4): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
regulation of transcription by RNA polymerase II	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
nuclear lumen	2
nervous system development	1
system development	1
spinal cord motor neuron differentiation	1
neuron fate specification	1
pancreas development	1
endocrine system development	1
anatomical structure development	1
neuron projection development	1
plasma membrane bounded cell projection morphogenesis	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
chromatin	1
DNA-binding transcription factor activity	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
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
chromosome	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
cytoplasm	1

Protein interactions and networks

STRING

1166 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MNX1	ISL1	P20663	883
MNX1	LMBR1	Q8WVP7	857
MNX1	ISL2	Q96A47	808
MNX1	GDF11	O95390	757
MNX1	RFX6	Q8HWS3	753
MNX1	OLIG2	Q13516	730
MNX1	SHH	Q15465	719
MNX1	GDPD5	Q8WTR4	717
MNX1	PTF1A	Q7RTS3	695
MNX1	LHX3	Q9UBR4	668
MNX1	NEUROG3	Q9Y4Z2	667
MNX1	SLC2A2	P11168	658
MNX1	NEUROD1	Q13562	633
MNX1	FOXA2	Q9Y261	606
MNX1	GCG	P01275	596

IntAct

23 interactions, top by confidence:

A	B	Type	Score
NFIC	NFIB	psi-mi:“MI:2364”(proximity)	0.690
ETV7	NFIB	psi-mi:“MI:2364”(proximity)	0.470
MNX1	SEC22B	psi-mi:“MI:0915”(physical association)	0.400
MNX1	RRBP1	psi-mi:“MI:0915”(physical association)	0.400
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
TBXT	BCL9	psi-mi:“MI:2364”(proximity)	0.270
ELK3	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
FEV	TAF4	psi-mi:“MI:2364”(proximity)	0.270
IRF4	ARID1A	psi-mi:“MI:2364”(proximity)	0.270
LHX3	BCL9	psi-mi:“MI:2364”(proximity)	0.270
NFIA	BCL9	psi-mi:“MI:2364”(proximity)	0.270
PAX6	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
PAX7	BCL9	psi-mi:“MI:2364”(proximity)	0.270
PAX8	BCL9	psi-mi:“MI:2364”(proximity)	0.270
PAX9	BCL9	psi-mi:“MI:2364”(proximity)	0.270
SOX15	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
SOX2	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
SP7	IGF2BP3	psi-mi:“MI:2364”(proximity)	0.270
TBR1	BCL9	psi-mi:“MI:2364”(proximity)	0.270
TLX1	BCL9	psi-mi:“MI:2364”(proximity)	0.270
TLX2	IGF2BP3	psi-mi:“MI:2364”(proximity)	0.270
TLX3	BCL9	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (33): MNX1 (Affinity Capture-RNA), MNX1 (Affinity Capture-RNA), MNX1 (Proximity Label-MS), RRBP1 (Proximity Label-MS), MNX1 (Proximity Label-MS), MNX1 (Proximity Label-MS), MNX1 (Proximity Label-MS), MNX1 (Proximity Label-MS), MNX1 (Proximity Label-MS), MNX1 (Proximity Label-MS), MNX1 (Proximity Label-MS), MNX1 (Proximity Label-MS), MNX1 (Proximity Label-MS), MNX1 (Proximity Label-MS), MNX1 (Proximity Label-MS)

ESM2 similar proteins: A0JPN1, A6NHT5, A6YP92, A7MB54, M0R6D8, O02786, O35085, O35762, O42230, O57601, O88181, O95096, P09065, P13297, P28360, P42581, P43697, P50219, P52955, P70390, P78414, P78415, P79772, P81067, P81068, Q05925, Q0P4W6, Q14549, Q14774, Q1XID0, Q2VL76, Q2VL77, Q2VL78, Q2VL79, Q2VL80, Q2VL82, Q2VL83, Q2VL84, Q2VL85, Q2VL86

Diamond homologs: A0JPN1, A1YG85, A5PKG8, A6NJ46, A6NMT0, A7MB54, A9L937, B0VXK3, D2KQB0, E7FDX5, M0R6D8, O08686, O13023, O35762, O42365, O43364, O43711, O55144, O88181, O93366, O93367, O93590, P0C1T1, P10035, P14652, P14837, P20009, P28468, P31245, P31246, P31261, P31314, P42583, P42584, P43120, P43345, P43688, P50219, P52945, P52950

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
GSK3B	down-regulates	MNX1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 29 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.

GO biological processes:

GO term	Partners	Fold	FDR
transcription by RNA polymerase II	6	14.6×	2e-04
brain development	5	13.7×	9e-04
chromatin remodeling	5	12.6×	1e-03
nervous system development	5	7.9×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	32
Likely pathogenic	13
Uncertain significance	237
Likely benign	111
Benign	16

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1338372	NM_005515.4(MNX1):c.874C>T (p.Arg292Trp)	Pathogenic
1338384	NM_005515.4(MNX1):c.752del (p.Gln251fs)	Pathogenic
1386281	NM_005515.4(MNX1):c.600_609del (p.Ile201fs)	Pathogenic
1452803	NM_005515.4(MNX1):c.686del (p.Phe229fs)	Pathogenic
1458016	NM_005515.4(MNX1):c.469dup (p.Ala157fs)	Pathogenic
1458729	NM_005515.4(MNX1):c.9dup (p.Ser4fs)	Pathogenic
1459648	NM_005515.4(MNX1):c.372_373insCCGCC (p.Ala125fs)	Pathogenic
14850	NM_005515.4(MNX1):c.570del (p.Gly191fs)	Pathogenic
14851	NM_005515.4(MNX1):c.775C>T (p.Gln259Ter)	Pathogenic
14852	NM_005515.4(MNX1):c.340del (p.His114fs)	Pathogenic
14855	NM_005515.4(MNX1):c.853-2A>G	Pathogenic
14858	MNX1, 24-BP DEL/2-BP INS, NT577	Pathogenic
1685952	NM_005515.4(MNX1):c.562C>T (p.Gln188Ter)	Pathogenic
1699254	NM_005515.4(MNX1):c.863G>A (p.Trp288Ter)	Pathogenic
2006188	NM_005515.4(MNX1):c.599_600dup (p.Ile201fs)	Pathogenic
2009332	NM_005515.4(MNX1):c.853-2A>C	Pathogenic
2095403	NM_005515.4(MNX1):c.697del (p.Ala233fs)	Pathogenic
2136634	NM_005515.4(MNX1):c.336dup (p.Pro113fs)	Pathogenic
2663031	NM_005515.4(MNX1):c.-11_276del (p.Met1fs)	Pathogenic
2853976	NM_005515.4(MNX1):c.321_333del (p.Gly109fs)	Pathogenic
3392972	NM_005515.4(MNX1):c.638G>A (p.Trp213Ter)	Pathogenic
3594481	NM_005515.4(MNX1):c.70C>T (p.Gln24Ter)	Pathogenic
3638448	NM_005515.4(MNX1):c.751C>T (p.Gln251Ter)	Pathogenic
3653129	NM_005515.4(MNX1):c.22del (p.Arg8fs)	Pathogenic
3658790	NM_005515.4(MNX1):c.196_211del (p.Pro66fs)	Pathogenic
435883	NM_005515.4(MNX1):c.53dup (p.Arg19fs)	Pathogenic
449412	NM_005515.4(MNX1):c.77del (p.Ala26fs)	Pathogenic
452317	NM_005515.4(MNX1):c.325_337del (p.Gly109fs)	Pathogenic
4726455	NM_005515.4(MNX1):c.568C>T (p.Gln190Ter)	Pathogenic
4736518	NM_005515.4(MNX1):c.378_384dup (p.Ala129fs)	Pathogenic

SpliceAI

479 predictions. Top by Δscore:

Variant	Effect	Δscore
7:157005872:ACC:A	acceptor_loss	1.0000
7:157005874:C:CC	acceptor_gain	1.0000
7:157006475:GCACC:G	donor_loss	1.0000
7:157006476:CACC:C	donor_loss	1.0000
7:157006478:C:G	donor_loss	1.0000
7:157006635:CTGGG:C	acceptor_gain	1.0000
7:157006638:GG:G	acceptor_gain	1.0000
7:157006640:C:CC	acceptor_gain	1.0000
7:157009656:TCACA:T	donor_loss	1.0000
7:157009657:CACA:C	donor_loss	1.0000
7:157009658:A:AC	donor_gain	1.0000
7:157009659:C:CC	donor_gain	1.0000
7:157009659:CA:C	donor_gain	1.0000
7:157009659:CAG:C	donor_gain	1.0000
7:157005869:TTCAC:T	acceptor_gain	0.9900
7:157005871:CAC:C	acceptor_gain	0.9900
7:157005872:AC:A	acceptor_gain	0.9900
7:157005873:CC:C	acceptor_gain	0.9900
7:157006636:TGGG:T	acceptor_gain	0.9900
7:157006637:GGG:G	acceptor_gain	0.9900
7:157009652:GTACT:G	donor_loss	0.9900
7:157009654:ACTC:A	donor_loss	0.9900
7:157009659:CAGT:C	donor_gain	0.9900
7:157005870:TCAC:T	acceptor_gain	0.9800
7:157005871:CACC:C	acceptor_gain	0.9800
7:157006473:GCGCA:G	donor_loss	0.9800
7:157006477:A:AC	donor_gain	0.9800
7:157006478:C:CC	donor_gain	0.9800
7:157009651:GGTAC:G	donor_loss	0.9800
7:157009653:TAC:T	donor_loss	0.9800

AlphaMissense

2559 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:157005833:C:G	R298P	1.000
7:157005834:G:A	R298C	1.000
7:157005834:G:C	R298G	1.000
7:157005834:G:T	R298S	1.000
7:157005835:T:A	K297N	1.000
7:157005835:T:G	K297N	1.000
7:157005836:T:A	K297I	1.000
7:157005836:T:G	K297T	1.000
7:157005837:T:C	K297E	1.000
7:157005838:C:A	W296C	1.000
7:157005838:C:G	W296C	1.000
7:157005840:A:G	W296R	1.000
7:157005840:A:T	W296R	1.000
7:157005841:T:A	K295N	1.000
7:157005841:T:G	K295N	1.000
7:157005842:T:A	K295I	1.000
7:157005842:T:G	K295T	1.000
7:157005843:T:C	K295E	1.000
7:157005843:T:G	K295Q	1.000
7:157005844:C:A	M294I	1.000
7:157005844:C:G	M294I	1.000
7:157005844:C:T	M294I	1.000
7:157005845:A:C	M294R	1.000
7:157005845:A:G	M294T	1.000
7:157005845:A:T	M294K	1.000
7:157005848:C:G	R293P	1.000
7:157005848:C:T	R293Q	1.000
7:157005849:G:A	R293W	1.000
7:157005849:G:C	R293G	1.000
7:157005851:C:A	R292L	1.000

dbSNP variants (sampled 300 via entrez): RS1000130205 (7:157004772 G>A), RS1000518471 (7:157005041 G>A,C,T), RS1001255929 (7:157005135 T>G), RS1001276222 (7:157005453 G>A,T), RS1001543943 (7:157007711 G>A), RS1001884205 (7:157006704 C>T), RS1001950686 (7:157007955 A>C), RS1002274390 (7:157006372 G>A,T), RS1002302115 (7:157011599 C>T), RS1002333153 (7:157011332 G>T), RS1002551728 (7:157009091 C>T), RS1003119436 (7:157008823 C>A), RS1003155663 (7:157008632 T>C), RS1004846312 (7:157010641 G>A,C), RS1004996052 (7:157004748 G>A)

Disease associations

OMIM: gene MIM:142994 | disease phenotypes: MIM:176450

GenCC curated gene-disease

Disease	Classification	Inheritance
Currarino triad	Definitive	Autosomal dominant
neonatal diabetes mellitus	Strong	Autosomal recessive
permanent neonatal diabetes mellitus	Strong	Autosomal recessive

Mondo (3): Currarino triad (MONDO:0008305), neonatal diabetes mellitus (MONDO:0016391), permanent neonatal diabetes mellitus (MONDO:0100164)

Orphanet (1): Currarino syndrome (Orphanet:1552)

HPO phenotypes

42 total (30 of 42 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000011	Neurogenic bladder
HP:0000020	Urinary incontinence
HP:0000076	Vesicoureteral reflux
HP:0000085	Horseshoe kidney
HP:0000125	Pelvic kidney
HP:0000143	Rectovaginal fistula
HP:0000238	Hydrocephalus
HP:0000813	Bicornuate uterus
HP:0001153	Septate vagina
HP:0001263	Global developmental delay
HP:0001287	Meningitis
HP:0002023	Anal atresia
HP:0002025	Anal stenosis
HP:0002144	Tethered cord
HP:0002242	Abnormal intestine morphology
HP:0002617	Vascular dilatation
HP:0003270	Abdominal distention
HP:0003419	Low back pain
HP:0003577	Congenital onset
HP:0003829	Typified by incomplete penetrance
HP:0004796	Gastrointestinal obstruction
HP:0007293	Anterior sacral meningocele
HP:0008517	Aplasia/Hypoplasia of the sacrum
HP:0009789	Perianal abscess
HP:0009790	Hemisacrum
HP:0009791	Bifid sacrum
HP:0009793	Presacral teratoma
HP:0010305	Absence of the sacrum

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST004773_4	Type 2 diabetes	2.000000e-08
GCST007847_115	Type 2 diabetes	1.000000e-08
GCST007847_60	Type 2 diabetes	3.000000e-07
GCST007847_66	Type 2 diabetes	6.000000e-07
GCST009379_79	Type 2 diabetes	2.000000e-17
GCST009391_1968	Metabolite levels	2.000000e-06
GCST010118_158	Type 2 diabetes	2.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010541	trimethylamine-N-oxide measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C536221	Currarino triad (supp.)
C563425	Diabetes Mellitus, Permanent Neonatal (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, increases methylation	5
mercuric bromide	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Tretinoin	affects expression, affects cotreatment, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
FR900359	decreases phosphorylation	1
apocarotenal	increases expression	1
bisphenol A	affects methylation	1
titanium dioxide	decreases expression	1
9,10-dihydro-9,10-dihydroxybenzo(a)pyrene	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
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Carbamazepine	affects expression	1
Cisplatin	affects cotreatment, increases expression	1
Cycloheximide	decreases expression, decreases reaction	1
Plant Extracts	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	decreases expression, decreases reaction	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
beta Carotene	increases expression	1

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A4E6	SEES3-1V human MNX1, clone1	Embryonic stem cell	Male
CVCL_A4E7	SEES3-1V human MNX1, clone2	Embryonic stem cell	Male
CVCL_A4E8	SEES3-1V human MNX1, clone3	Embryonic stem cell	Male
CVCL_F1TN	HyCyte SNU-1 KO-hMNX1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02624817	PHASE4	COMPLETED	Long-Term Sulfonylurea Response in KCNJ11 Neonatal Diabetes
NCT02624830	PHASE4	UNKNOWN	Long-Term Sulfonylurea Response in ABCC8 Neonatal Diabetes (SuResponsSUR)
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT00780117	Not specified	COMPLETED	Characterization of At-risk Population for Pre-sacral Tumor in CURRARINO Syndrome