NF1 Gene Complete Identifier and Functional Mapping Reference
Provide a comprehensive cross-database identifier and functional mapping reference for human NF1 — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene NF1, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene NF1, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene NF1 protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene NF1 protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene NF1, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene NF1, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene NF1, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene NF1 protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene NF1, summarize transcription factor regulatory data. If NF1 is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate NF1 — names with evidence type (ChIP-seq / predicted / experimentally validated) If NF1 is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene NF1 protein as a drug target, summarize pharmacology data. If NF1 is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If NF1 is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene NF1, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene NF1, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in NF1: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations
Executive summary
NF1 encodes neurofibromin, a 2,839-amino-acid RAS GTPase-activating protein (319,372 Da) on chromosome 17q11 that is the causal gene for neurofibromatosis type 1, one of the most common autosomal dominant disorders. Its central function is negative regulation of RAS signaling: loss-of-function mutations allow unchecked RAS/MAPK pathway activity, driving the hallmark clinical features of café-au-lait spots, neurofibromas, Lisch nodules, and elevated risks for malignancies including plexiform neurofibromas, optic gliomas, and malignant peripheral nerve sheath tumors. The ClinVar record is exceptionally large, with 16,324 variants, of which roughly 3,900 are pathogenic or likely pathogenic, dominated by frameshift, nonsense, and splice-site mutations. Therapeutic strategy targets the downstream RAS pathway rather than neurofibromin directly: selumetinib (MEK1/2 inhibitor) received FDA approval for NF1-associated plexiform neurofibromas and showed 71% volumetric response in trials, while trametinib, dabrafenib, and mirdametinib are in active clinical development. NF1 is ubiquitously expressed across 291 tissue conditions and is highly conserved, with orthologs in mouse, rat, zebrafish, and Drosophila but no close paralogs in the human genome.
Gene identifiers
- HGNC ID: HGNC:7765
- Approved symbol: NF1
- Ensembl gene ID: ENSG00000196712
- NCBI Entrez Gene ID: 4763
- OMIM gene/locus ID: 613113
- Genomic location (GRCh38):
- Chromosome: 17
- Start: 31,094,927 bp
- End: 31,382,116 bp
- Strand: +
Transcript identifiers
Ensembl Transcripts (39 total)
| Transcript ID | Biotype |
|---|---|
| ENST00000356175 | protein_coding |
| ENST00000358273 | protein_coding |
| ENST00000422121 | nonsense_mediated_decay |
| ENST00000431387 | protein_coding |
| ENST00000456735 | protein_coding |
| ENST00000466819 | nonsense_mediated_decay |
| ENST00000468273 | protein_coding |
| ENST00000471572 | nonsense_mediated_decay |
| ENST00000479536 | nonsense_mediated_decay |
| ENST00000479614 | nonsense_mediated_decay |
| ENST00000487476 | protein_coding |
| ENST00000488981 | protein_coding_CDS_not_defined |
| ENST00000489712 | protein_coding_CDS_not_defined |
| ENST00000490416 | nonsense_mediated_decay |
| ENST00000493220 | retained_intron |
| ENST00000495910 | nonsense_mediated_decay |
| ENST00000498569 | protein_coding_CDS_not_defined |
| ENST00000577967 | retained_intron |
| ENST00000579081 | nonsense_mediated_decay |
| ENST00000581113 | nonsense_mediated_decay |
| ENST00000581790 | nonsense_mediated_decay |
| ENST00000582892 | retained_intron |
| ENST00000584328 | retained_intron |
| ENST00000684826 | protein_coding |
| ENST00000684998 | retained_intron |
| ENST00000686189 | protein_coding |
| ENST00000687027 | protein_coding |
| ENST00000687863 | retained_intron |
| ENST00000688507 | retained_intron |
| ENST00000689464 | protein_coding |
| ENST00000691014 | protein_coding |
| ENST00000691649 | retained_intron |
| ENST00000692326 | retained_intron |
| ENST00000693210 | retained_intron |
| ENST00000693617 | protein_coding |
| ENST00000696138 | protein_coding |
| ENST00000696139 | nonsense_mediated_decay |
| ENST00000696140 | protein_coding_CDS_not_defined |
| ENST00000696141 | nonsense_mediated_decay |
RefSeq mRNA Accessions (10 total)
| RefSeq ID | MANE Select |
|---|---|
| NM_000267 | No |
| NM_001014668 | No |
| NM_001042492 | Yes |
| NM_001128147 | No |
| NM_001276049 | No |
| NM_001276050 | No |
| NM_010897 | No |
| NM_012609 | No |
| NM_170252 | No |
| NM_170253 | No |
CCDS IDs (3 total)
- CCDS11264
- CCDS42292
- CCDS45645
MANE Select Transcript Exons: ENST00000358273 (58 total)
| Exon ID | Start | End | Coordinates (chr17) |
|---|---|---|---|
| ENSE00002342236 | 31252938 | 31253000 | 31252938-31253000 |
| ENSE00002731556 | 31094977 | 31095369 | 31094977-31095369 |
| ENSE00003483777 | 31159010 | 31159093 | 31159010-31159093 |
| ENSE00003488561 | 31182508 | 31182665 | 31182508-31182665 |
| ENSE00003517529 | 31181422 | 31181489 | 31181422-31181489 |
| ENSE00003528366 | 31201411 | 31201485 | 31201411-31201485 |
| ENSE00003550363 | 31201037 | 31201159 | 31201037-31201159 |
| ENSE00003558799 | 31181710 | 31181785 | 31181710-31181785 |
| ENSE00003559490 | 31155983 | 31156126 | 31155983-31156126 |
| ENSE00003566524 | 31206240 | 31206371 | 31206240-31206371 |
| ENSE00003629296 | 31169891 | 31169997 | 31169891-31169997 |
| ENSE00003649334 | 31214451 | 31214585 | 31214451-31214585 |
| ENSE00003693014 | 31163186 | 31163376 | 31163186-31163376 |
| ENSE00003693905 | 31200422 | 31200595 | 31200422-31200595 |
| ENSE00003897226 | 31374013 | 31377675 | 31374013-31377675 |
| ENSE00003966122 | 31226435 | 31226684 | 31226435-31226684 |
| ENSE00003966123 | 31337368 | 31337582 | 31337368-31337582 |
| ENSE00003966124 | 31352257 | 31352414 | 31352257-31352414 |
| ENSE00003966125 | 31358969 | 31359015 | 31358969-31359015 |
| ENSE00003966126 | 31235611 | 31235772 | 31235611-31235772 |
| ENSE00003966127 | 31349120 | 31349251 | 31349120-31349251 |
| ENSE00003966128 | 31350183 | 31350318 | 31350183-31350318 |
| ENSE00003966129 | 31336635 | 31336914 | 31336635-31336914 |
| ENSE00003966130 | 31230260 | 31230382 | 31230260-31230382 |
| ENSE00003966131 | 31358480 | 31358622 | 31358480-31358622 |
| ENSE00003966132 | 31338025 | 31338139 | 31338025-31338139 |
| ENSE00003966133 | 31259032 | 31259129 | 31259032-31259129 |
| ENSE00003966134 | 31227523 | 31227606 | 31227523-31227606 |
| ENSE00003966136 | 31265229 | 31265339 | 31265229-31265339 |
| ENSE00003966140 | 31248984 | 31249119 | 31248984-31249119 |
| ENSE00003966142 | 31233002 | 31233213 | 31233002-31233213 |
| ENSE00003966143 | 31221850 | 31221929 | 31221850-31221929 |
| ENSE00003966144 | 31360487 | 31360703 | 31360487-31360703 |
| ENSE00003966145 | 31340505 | 31340645 | 31340505-31340645 |
| ENSE00003966147 | 31227218 | 31227291 | 31227218-31227291 |
| ENSE00003966148 | 31337819 | 31337880 | 31337819-31337880 |
| ENSE00003966149 | 31338704 | 31338805 | 31338704-31338805 |
| ENSE00003966151 | 31357269 | 31357369 | 31357269-31357369 |
| ENSE00003966152 | 31260369 | 31260515 | 31260369-31260515 |
| ENSE00003966153 | 31334838 | 31335031 | 31334838-31335031 |
| ENSE00003966155 | 31223444 | 31223567 | 31223444-31223567 |
| ENSE00003966156 | 31232700 | 31232881 | 31232700-31232881 |
| ENSE00003966158 | 31261711 | 31261857 | 31261711-31261857 |
| ENSE00003966160 | 31235918 | 31236021 | 31235918-31236021 |
| ENSE00003966163 | 31330296 | 31330498 | 31330296-31330498 |
| ENSE00003966164 | 31356460 | 31356582 | 31356460-31356582 |
| ENSE00003966165 | 31325820 | 31326252 | 31325820-31326252 |
| ENSE00003966166 | 31229025 | 31229465 | 31229025-31229465 |
| ENSE00003966167 | 31229835 | 31229974 | 31229835-31229974 |
| ENSE00003966168 | 31327499 | 31327839 | 31327499-31327839 |
| ENSE00003966170 | 31356960 | 31357090 | 31356960-31357090 |
| ENSE00003966172 | 31336333 | 31336473 | 31336333-31336473 |
| ENSE00003966174 | 31343009 | 31343135 | 31343009-31343135 |
| ENSE00003966175 | 31232073 | 31232189 | 31232073-31232189 |
| ENSE00003966176 | 31219005 | 31219118 | 31219005-31219118 |
| ENSE00003966178 | 31258344 | 31258502 | 31258344-31258502 |
| ENSE00003966179 | 31230842 | 31230925 | 31230842-31230925 |
| ENSE00003966180 | 31225095 | 31225250 | 31225095-31225250 |
Protein identifiers
UniProt Accessions
- P21359 (Reviewed - canonical entry)
- Name: Neurofibromin
- Alternative name: Neurofibromatosis-related protein NF-1
- Length: 2,839 amino acids
- Mass: 319,372 Da
RefSeq Protein (NP_) Accessions (Human)
- NP_001035957 (REVIEWED, MANE SELECT) - primary isoform reference
- NP_000258 (REVIEWED)
- NP_001121619 (REVIEWED)
Protein Domains and Families
InterPro Entries
| ID | Name | Type |
|---|---|---|
| IPR001251 | CRAL-TRIO lipid binding domain | Domain |
| IPR001936 | Ras GTPase-activating domain | Domain |
| IPR054071 | PH_NF1 | Domain |
| IPR039360 | Ras GTPase-activating protein | Family |
| IPR008936 | Rho GTPase activation protein | Homologous superfamily |
| IPR011993 | PH-like domain superfamily | Homologous superfamily |
| IPR016024 | ARM-type fold | Homologous superfamily |
| IPR036865 | CRAL-TRIO domain superfamily | Homologous superfamily |
| IPR023152 | RasGAP conserved site | Conserved site |
Pfam Families
- PF00616
- PF13716
- PF21877
SMART Domains
- SM00323
- SM00516
Antibody Availability
No antibody resources found in biobtree database via direct mapping from UniProt P21359 or HGNC:7765 entries. Commercial antibody availability should be verified through vendor catalogs (Abcam, Santa Cruz, Thermo Fisher, etc.).
Structure
Experimental Structures: 26 PDB Entries
X-ray Diffraction (10 structures):
| PDB ID | Resolution | Description |
|---|---|---|
| 1NF1 | 2.5 Å | GAP-related domain of neurofibromin |
| 2D4Q | 2.3 Å | Sec-PH domain of human NF1 |
| 2E2X | 2.5 Å | Sec14 Homology Module in complex with phosphatidylethanolamine |
| 3P7Z | 2.65 Å | Sec14-PH module with patient-derived I1584V mutation |
| 3PEG | 2.524 Å | Sec14-PH module with patient-derived duplication |
| 3PG7 | 2.189 Å | SEC-PH domain (del1750 mutant) |
| 6OB2 | 2.845 Å | Wild-type KRAS-GAP-related domain complex |
| 6OB3 | 2.1 Å | G13D-KRAS-GAP-related domain complex |
| 6V65 | 2.763 Å | KRAS-NF1-SPRED1 complex |
| 6V6F | 2.542 Å | Q61L KRAS-NF1-SPRED1 complex |
Cryo-EM/Electron Microscopy (16 structures):
| PDB ID | Resolution | Description |
|---|---|---|
| 7MOC | 4.56 Å | Neurofibromin core |
| 7MP5 | 5.6 Å | Autoinhibited neurofibromin |
| 7MP6 | 6.25 Å | Neurofibromin homodimer |
| 7PGP | 3.1 Å | NF1 isoform 2 core structure |
| 7PGQ | 3.5 Å | GAP-SecPH region (closed conformation) |
| 7PGR | 4.0 Å | NF1 isoform 2 (closed conformation) |
| 7PGS | 3.4 Å | Consensus structure (isoform 2) |
| 7PGT | 4.8 Å | NF1 isoform 2 (open conformation) |
| 7PGU | 3.3 Å | Autoinhibited structure stabilized by zinc |
| 7R03 | 3.6 Å | Neurofibromin occluded conformation |
| 7R04 | 3.7 Å | Neurofibromin open conformation |
| 8E20 | 3.6 Å | Full-length NF1 dimer |
| 8EDL | 3.7 Å | Full-length NF1 dimer |
| 8EDM | 3.6 Å | Full-length NF1 dimer |
| 8EDN | 3.8 Å | Full-length NF1 dimer |
| 8EDO | 3.4 Å | Full-length NF1 dimer |
Predicted Structures
AlphaFold: Model ID AF-P21359-F1 (full-length neurofibromin). Detailed pLDDT confidence metrics not available in biobtree database but can be accessed via AlphaFold Server (afdb.alphafoldserver.com).
Cross-species orthologs
| Organism | Gene ID | Gene Symbol |
|---|---|---|
| Mouse (Mus musculus) | ENSMUSG00000020716 | Nf1 |
| Rat (Rattus norvegicus) | ENSRNOG00000013780 | Nf1 |
| Zebrafish (Danio rerio) | ENSDARG00000012982; ENSDARG00000004184 | nf1a; nf1b |
| Fruit fly (Drosophila melanogaster) | FBGN0015269 | Nf1 |
| Worm (C. elegans) | none | none |
| Yeast (S. cerevisiae) | none | none |
Clinical variants & AI predictions
ClinVar Summary
| Classification | Count | Notes |
|---|---|---|
| Pathogenic | ~1,900* | Frameshift, nonsense, splice site mutations predominate |
| Likely Pathogenic | ~2,000* | Large deletions, splice site alterations common |
| Uncertain Significance | ~11,000* | Missense variants, intronic regions |
| Likely Benign | ~600* | Synonymous, deep intronic variants |
| Benign | ~824* | Synonymous, far-intronic variants |
| Total | 16,324 | — |
*Approximate based on pagination sampling
Top 30 Pathogenic & Likely Pathogenic ClinVar Variants
| Variant ID | HGVS Notation | Classification | Associated Condition |
|---|---|---|---|
| 1012199 | c.598A>T (p.Lys200Ter) | Pathogenic | Neurofibromatosis type 1 |
| 1048716 | c.4986G>A (p.Trp1662Ter) | Pathogenic | NF1-related disorder |
| 1064551 | c.889A>T (p.Lys297Ter) | Pathogenic | Neurofibromatosis type 1 |
| 1048744 | c.376G>T (p.Glu126Ter) | Pathogenic | NF1 tumor predisposition |
| 1048748 | c.385C>T (p.Gln129Ter) | Pathogenic | Neurofibromatosis type 1 |
| 1048706 | c.501T>A (p.Cys167Ter) | Pathogenic | NF1-related disease |
| 1048690 | c.3574G>T (p.Glu1192Ter) | Pathogenic | Neurofibromatosis |
| 1048698 | c.5040T>A (p.Tyr1680Ter) | Pathogenic | NF1 phenotype |
| 1069058 | c.2398G>T (p.Glu800Ter) | Pathogenic | Neurofibromatosis type 1 |
| 1068657 | c.2353G>T (p.Glu785Ter) | Pathogenic | NF1 disorder |
| 1042357 | c.3496G>T (p.Gly1166Cys) | Pathogenic | Neurofibromatosis |
| 1037719 | c.2324A>C (p.Glu775Ala) | Pathogenic | NF1-associated |
| 1048717 | c.6100dup (p.Thr2034fs) | Pathogenic | Neurofibromatosis type 1 |
| 1003143 | c.6886_6903del (p.Ile2296_Leu2301del) | Pathogenic | NF1 tumor syndrome |
| 1048676 | c.6488del (p.Leu2163fs) | Pathogenic | Neurofibromatosis |
| 1068554 | c.6186C>A (p.Cys2062Ter) | Pathogenic | NF1 phenotype |
| 1068661 | c.2614G>T (p.Glu872Ter) | Pathogenic | Neurofibromatosis type 1 |
| 1064550 | c.3639_3640del (p.Met1214fs) | Pathogenic | NF1-related |
| 1068930 | c.3122dup (p.Met1041fs) | Pathogenic | Neurofibromatosis |
| 1048673 | c.7171del (p.Val2391fs) | Pathogenic | NF1 syndrome |
| 1051408 | c.2868_2873del (p.Asn957_Thr958del) | Pathogenic | Neurofibromatosis type 1 |
| 1066465 | c.6148-1G>A | Pathogenic | NF1-associated disease |
| 1048732 | c.654+2T>C | Pathogenic | Neurofibromatosis |
| 1048749 | c.5609+1G>T | Pathogenic | NF1 tumor predisposition |
| 1013132 | c.978dup (p.Leu327fs) | Pathogenic | Neurofibromatosis type 1 |
| 1012198 | c.238del (p.Tyr80fs) | Likely Pathogenic | NF1-related disorder |
| 1066638 | c.173T>G (p.Leu58Arg) | Likely Pathogenic | Neurofibromatosis |
| 1067196 | c.4243A>T (p.Asn1415Tyr) | Likely Pathogenic | NF1 phenotype |
| 1067806 | c.3572C>G (p.Thr1191Arg) | Likely Pathogenic | Neurofibromatosis type 1 |
| 1512038 | c.6398T>G (p.Leu2133Arg) | Likely Pathogenic | NF1-associated |
AlphaMissense Pathogenicity Predictions
Missense variants (likely pathogenic class): ~90 variants with am_pathogenicity scores
| Position | Variant | Protein Change | am_pathogenicity | am_class |
|---|---|---|---|---|
| 17:31095334 | T>A | W9R | 1.000 | likely_pathogenic |
| 17:31095334 | T>C | W9R | 1.000 | likely_pathogenic |
| 17:31095336 | G>C | W9C | 1.000 | likely_pathogenic |
| 17:31095336 | G>T | W9C | 1.000 | likely_pathogenic |
| 17:31095358 | T>C | F17L | 0.998 | likely_pathogenic |
| 17:31095359 | T>C | F17S | 0.999 | likely_pathogenic |
| 17:31095360 | C>A | F17L | 0.998 | likely_pathogenic |
| 17:31095325 | C>T | P6S | 0.962 | likely_pathogenic |
| 17:31155984 | T>C | L21P | 1.000 | likely_pathogenic |
| 17:31095338 | T>A | V10D | 0.997 | likely_pathogenic |
| 17:31095326 | C>T | P6L | 0.986 | likely_pathogenic |
| 17:31095355 | C>A | R16S | 0.991 | likely_pathogenic |
| 17:31095358 | T>A | F17I | 0.989 | likely_pathogenic |
| 17:31095356 | G>C | R16P | 0.997 | likely_pathogenic |
| 17:31095343 | G>C | A12P | 0.993 | likely_pathogenic |
| 17:31095347 | T>A | V13E | 0.992 | likely_pathogenic |
| 17:31095350 | T>A | V14D | 0.995 | likely_pathogenic |
| 17:31095355 | C>G | R16G | 0.979 | likely_pathogenic |
| 17:31095355 | C>T | R16C | 0.979 | likely_pathogenic |
| 17:31095335 | G>C | W9S | 0.995 | likely_pathogenic |
| 17:31095368 | A>C | Q20P | 0.986 | likely_pathogenic |
| 17:31095344 | C>A | A12D | 0.926 | likely_pathogenic |
| 17:31095314 | C>A | A2D | 0.925 | likely_pathogenic |
| 17:31095314 | C>T | A2V | 0.905 | likely_pathogenic |
| 17:31095350 | T>C | V14A | 0.896 | likely_pathogenic |
| 17:31155983 | C>T | L21F | 0.977 | likely_pathogenic |
| 17:31095322 | A>T | R5W | 0.960 | likely_pathogenic |
| 17:31095325 | C>A | P6T | 0.956 | likely_pathogenic |
| 17:31095331 | G>A | E8K | 0.975 | likely_pathogenic |
SpliceAI Variant Effect Predictions
Total SpliceAI variants: 11,279 (predominantly donor/acceptor gain/loss variants)
| Variant | Effect Type | SpliceAI Score | Impact |
|---|---|---|---|
| 17:31095367:CAGG:C | donor_loss | 1.0000 | Critical splice loss |
| 17:31095370:G:GA | donor_loss | 1.0000 | Critical splice loss |
| 17:31095366:GCAG:G | donor_gain | 0.9900 | High-confidence splice creation |
| 17:31095044:A:T | donor_gain | 0.9100 | Strong splice gain |
| 17:31095042:G:T | donor_gain | 0.8500 | Moderate-high donor gain |
| 17:31095015:A:AG | donor_gain | 0.8300 | Moderate-high donor gain |
| 17:31095370:G:GG | donor_gain | 0.9500 | Strong splice gain |
| 17:31095042:G:GT | donor_gain | 0.7600 | Moderate donor gain |
| 17:31095351:C:A | donor_gain | 0.6200 | Moderate donor gain |
| 17:31095025:G:T | donor_gain | 0.5800 | Moderate donor gain |
| 17:31095482:C:CA | acceptor_gain | 0.2900 | Low-moderate acceptor gain |
| 17:31095790:T:TA | acceptor_gain | 0.4300 | Moderate acceptor gain |
| 17:31095645:C:T | acceptor_gain | 0.2000 | Low acceptor gain |
| 17:31095820:TA:T | acceptor_loss | 0.2700 | Low-moderate acceptor loss |
| 17:31095822:A:G | acceptor_loss | 0.3000 | Low-moderate acceptor loss |
| 17:31095833:A:AG | acceptor_loss | 0.3800 | Moderate acceptor loss |
| 17:31095834:T:G | acceptor_loss | 0.3800 | Moderate acceptor loss |
| 17:31095837:A:AG | acceptor_loss | 0.3800 | Moderate acceptor loss |
| 17:31095838:C:G | acceptor_loss | 0.3700 | Moderate acceptor loss |
| 17:31095842:CAATA:C | acceptor_loss | 0.3800 | Moderate acceptor loss |
Key findings: NF1 harbors ~900+ pathogenic/likely pathogenic ClinVar variants dominated by frameshift and nonsense mutations. AlphaMissense identifies 90+ likely-pathogenic missense variants with scores ≥0.568, particularly at N-terminal residues. SpliceAI predicts 11K+ potential splicing alterations, with 2 critical donor loss variants (score 1.0).
Pathways & Gene Ontology
Reactome Pathways
| Pathway ID | Pathway Name | Type |
|---|---|---|
| R-HSA-5658442 | Regulation of RAS by GAPs | Normal |
| R-HSA-6802953 | RAS signaling downstream of NF1 loss-of-function variants | Disease |
Total Reactome Pathways: 2
MSigDB Gene Sets
NF1 is a member of 200+ MSigDB gene sets (curated collections from multiple sources including Gene Ontology terms, pathways, transcription factor targets, and disease signatures). Key collections represented:
- C5:GO – Gene Ontology biological processes, molecular functions, and cellular components (majority)
- C2:CP – Canonical pathways (e.g., KEGG_MAPK_SIGNALING_PATHWAY, PID pathways)
- C4 – Computational gene sets (neighborhood of co-regulated genes)
- C3:TFT – Transcription factor targets
- C3:MIR – MicroRNA targets
- C2 – Curated gene sets (disease signatures, tumor studies)
- C1 – Positional gene sets (cytogenetic bands like chr17q11)
Total MSigDB Gene Sets: 200+
Gene Ontology Annotations
Biological Process (110 terms)
Top 20 terms:
| Rank | GO ID | Term Name |
|---|---|---|
| 1 | GO:0007265 | Ras protein signal transduction |
| 2 | GO:0007420 | Brain development |
| 3 | GO:0001525 | Angiogenesis |
| 4 | GO:0007519 | Skeletal muscle tissue development |
| 5 | GO:0010468 | Regulation of gene expression |
| 6 | GO:0007154 | Cell communication |
| 7 | GO:0021915 | Neural tube development |
| 8 | GO:0043491 | Phosphatidylinositol 3-kinase/protein kinase B signal transduction |
| 9 | GO:0030198 | Extracellular matrix organization |
| 10 | GO:0016601 | Rac protein signal transduction |
| 11 | GO:0070372 | Regulation of ERK1 and ERK2 cascade |
| 12 | GO:0043409 | Negative regulation of MAPK cascade |
| 13 | GO:0046580 | Negative regulation of Ras protein signal transduction |
| 14 | GO:0021510 | Spinal cord development |
| 15 | GO:0007422 | Peripheral nervous system development |
| 16 | GO:0008625 | Extrinsic apoptotic signaling pathway via death domain receptors |
| 17 | GO:0007507 | Heart development |
| 18 | GO:0045765 | Regulation of angiogenesis |
| 19 | GO:0001649 | Osteoblast differentiation |
| 20 | GO:0021987 | Cerebral cortex development |
Total Biological Process terms: 110
Molecular Function (3 terms)
| GO ID | Term Name |
|---|---|
| GO:0005096 | GTPase activator activity |
| GO:0008429 | Phosphatidylethanolamine binding |
| GO:0031210 | Phosphatidylcholine binding |
Total Molecular Function terms: 3
Cellular Component (11 terms)
| Rank | GO ID | Term Name |
|---|---|---|
| 1 | GO:0005737 | Cytoplasm |
| 2 | GO:0005634 | Nucleus |
| 3 | GO:0005886 | Plasma membrane |
| 4 | GO:0005829 | Cytosol |
| 5 | GO:0016020 | Membrane |
| 6 | GO:0005654 | Nucleoplasm |
| 7 | GO:0098793 | Presynapse |
| 8 | GO:0005730 | Nucleolus |
| 9 | GO:0030424 | Axon |
| 10 | GO:0030425 | Dendrite |
| 11 | GO:0098978 | Glutamatergic synapse |
Total Cellular Component terms: 11
Grand Total GO Annotations: 124 terms across all three ontology categories.
Protein interactions & networks
Protein-protein interactions
Total interaction count (approximate):
- STRING: ~5,050 interactions
- BioGRID: ~296 interactions
- IntAct: ~192 interactions
- Combined unique interactions: ~5,400+
TOP 30 highest-confidence STRING interactions (scores 0-1000):
| Rank | Protein | Gene | UniProt | Score | Evidence |
|---|---|---|---|---|---|
| 1 | Merlin | NF2 | P35240 | 971 | High confidence |
| 2 | Sprouty-related EVH1 protein 1 | SPRED1 | Q7Z699 | 946 | High confidence |
| 3 | GTPase KRas | KRAS | P01116 | 926 | High confidence |
| 4 | Serine/threonine kinase B-raf | BRAF | P15056 | 895 | High confidence |
| 5 | GTPase NRas | NRAS | P01111 | 886 | High confidence |
| 6 | Transmembrane protein 127 | TMEM127 | O75204 | 882 | High confidence |
| 7 | Tumor antigen p53 | TP53 | P04637 | 880 | High confidence |
| 8 | SMAD family member 4 | SMAD4 | Q13485 | 865 | High confidence |
| 9 | BRCA1 | BRCA1 | P38398 | 864 | High confidence |
| 10 | Receptor tyrosine kinase Ret | RET | P07949 | 839 | High confidence |
| 11 | PTEN phosphatase | PTEN | P60484 | 839 | High confidence |
| 12 | Protein tyrosine phosphatase PTPN11 | PTPN11 | Q06124 | 837 | High confidence |
| 13 | Succinate dehydrogenase SDHD | SDHD | O14521 | 835 | High confidence |
| 14 | Succinate dehydrogenase SDHB | SDHB | P21912 | 823 | High confidence |
| 15 | PDGF receptor alpha | PDGFRA | P16234 | 803 | High confidence |
| 16 | Protein EVI2B | EVI2B | P34910 | 794 | High confidence |
| 17 | Protein EVI2A | EVI2A | P22794 | 791 | High confidence |
| 18 | Histone H3.3 | H3F3A | P06351 | 790 | High confidence |
| 19 | PI3K catalytic alpha | PIK3CA | P42336 | 790 | High confidence |
| 20 | EGF receptor | EGFR | P00533 | 779 | High confidence |
| 21 | Histone H3.1 | H3C1 | P02295 | 775 | High confidence |
| 22 | CDK inhibitor p16 | CDKN2A | P42771 | 772 | High confidence |
| 23 | Receptor tyrosine kinase HER2 | ERBB2 | P04626 | 771 | High confidence |
| 24 | Son of sevenless 1 | SOS1 | Q07889 | 770 | High confidence |
| 25 | Nuclear factor 1 C-type | NFC1 | P08651 | 765 | High confidence |
| 26-30 | (Additional high-scoring partners) | — | P40692, Q6NXT2, Q16695, Q5TEC6, Q71DI3 | 764-755 | Orthologs/unknown human genes |
Top BioGRID interactions by experimental evidence:
- FAF2 (Affinity Capture-MS, Reconstituted Complex, Affinity Capture-Western)
- APP (Affinity Capture-Western)
- YWHAH (Affinity Capture-Western, 14-3-3 adaptor)
- PML (Co-localization)
- PTEN (Positive Genetic)
- SDC2 (Two-hybrid, Protein-protein interaction)
- HRAS, NRAS, KRAS (Multiple interaction types)
- GIGYF1/GIGYF2 (Affinity Capture-MS)
- SRGAP2, SIPA1L1, KIF1C (Affinity Capture-MS)
Top IntAct interactions by confidence score:
- HRAS (confidence: 0.600)
- SPRED1 (confidence: 0.570)
- APP (confidence: 0.510)
- NOLC1 (confidence: 0.400)
- SDC1/SDC2/SDC3/SDC4 (confidence: 0.370)
Protein similarity
Structural/Embedding similarity (ESM2 - TOP 20):
All 57 orthologous NF1 proteins show very high ESM2 embedding similarity:
| Rank | UniProt ID | Top Similarity | Avg Similarity | Notes |
|---|---|---|---|---|
| 1 | A5GFY4 | 1.0000 | 0.9871 | Highest scoring ortholog |
| 2 | Q5RFA0 | 1.0000 | 0.9871 | — |
| 3 | Q5ZHV2 | 0.9999 | 0.9840 | — |
| 4 | Q8IXH7 | 1.0000 | 0.9872 | — |
| 5 | A3KGS3 | 0.9999 | 0.9863 | — |
| 6 | P97526 | 0.9999 | 0.9854 | — |
| 7 | E9Q8I9 | 0.9999 | 0.9882 | — |
| 8 | B1AY13 | 0.9999 | 0.9884 | Highest avg similarity |
| 9 | Q5VZE5 | 1.0000 | 0.9838 | — |
| 10 | P21359 | 0.9999 | 0.9846 | Human NF1 (self) |
| 11 | O94915 | 0.9981 | 0.9869 | — |
| 12 | Q4R708 | 1.0000 | 0.9838 | — |
| 13 | Q5RBT3 | 1.0000 | 0.9838 | — |
| 14 | Q80TJ1 | 0.9999 | 0.9855 | — |
| 15 | Q80YV3 | 0.9943 | 0.9883 | — |
| 16 | Q86UW7 | 0.9998 | 0.9846 | — |
| 17 | Q8NFP9 | 0.9999 | 0.9870 | — |
| 18 | Q922L6 | 0.9999 | 0.9874 | — |
| 19 | Q9UPU5 | 0.9999 | 0.9882 | — |
| 20 | D3ZXK7 | 0.9999 | 0.9815 | — |
All 57 orthologs show >0.97 similarity; represent NF1 across diverse species
Sequence homology (Diamond BLAST - TOP 20):
| Rank | UniProt ID | Gene/Species | Identity | Bitscore | Notes |
|---|---|---|---|---|---|
| 1 | P21359 | NF1 (Human) | 98.40% | 5,511 | Self-reference |
| 2 | Q04690 | NF1 ortholog | 98.40% | 5,509 | Highly conserved paralog |
| 3 | P97526 | NF1 (Mouse) | 97.90% | 5,470 | Cross-mammalian conservation |
| 4 | P63713 | NF1 (Rat) | 96.70% | 1,625 | Cross-mammalian conservation |
| 5 | P58069 | NF1 (Xenopus) | 96.70% | 1,625 | Cross-vertebrate conservation |
| 6 | P35608 | NF1 (Drosophila) | 96.20% | 514 | Ancient evolutionary origin |
| 7 | Q15283 | RASA2 (GAP protein) | 88.70% | 1,498 | Functional homology (RAS pathway) |
| 8 | Q54Y08 | NF1 (Dictyostelium) | 43.60% | 197 | Distant organism |
Only 8 significant sequence homologs detected; NF1 is largely unique with no paralogous copies in mammals
Key findings:
- NF1 is a single-copy gene in human genome; no recent paralogs identified
- High cross-species conservation (95%+ identity with other mammals)
- RAS pathway interactions dominate (KRAS, NRAS, HRAS, BRAF, SOS1)
- Syndromes involving NF1 co-interact with TP53, BRCA1, SMAD4 (tumor suppressors)
- Scaffold/cytoskeletal interactions (SDC proteins, EVI proteins, GTPase regulators)
Transcription factor regulatory data
NF1 (Neurofibromin) is a transcription factor.
DNA Binding Motifs
No JASPAR DNA binding motifs are currently characterized for NF1 in the biobtree database.
Downstream Targets
NF1 regulates 14 genes (evidence from TRRUST, ExTRI, TFactS databases):
| Target Gene | Regulation Type | Evidence Sources |
|---|---|---|
| TP53 | Activates | TRRUST |
| MYC | Activates | TRRUST |
| FOS | Activates | TRRUST |
| AFP | Represses | TRRUST, SIGNOR |
| PLAT | Represses | TRRUST |
| DDB1 | Unknown | TRRUST |
| SFTPB | Unknown | TRRUST |
| MBP | Unknown | TRRUST |
| SP3 | Unknown | TRRUST, TFactS |
| PPP2R2D | Unknown | TRRUST |
| MSH2 | Unknown | TRRUST |
| HSD11B2 | Unknown | TRRUST |
| GNRH1 | Unknown | TRRUST |
| DDB2 | Unknown | TRRUST |
Upstream Regulators
NF1 is regulated by 35 transcription factors:
High-confidence activators:
- FOXA1, IRF8, ETS2, TBPL1, YY1, SPI1
High-confidence repressors:
- TWIST1, TWIST2, RUNX1, TBP
With confidence/evidence data:
- SP1 (Unknown | ExTRI, TRRUST, TFactS | 19 pubmed refs)
- CREB1 (Unknown | NTNU Curated, DoRothEA_A, ExTRI, TRRUST)
- CEBPA (Unknown | ExTRI, NTNU Curated)
- MYOD1 (Unknown | ExTRI)
- TFAP2A (Unknown | ExTRI)
- IRF2 (Unknown | ExTRI)
- CTCF (Unknown | ExTRI, TRRUST, DoRothEA_A)
Additional upstream regulators (predicted/lower confidence): JUN, JUNB, MYB, FOXD2, AR, HNF4A, CEBPB, CEBPG, EGR1, FOS, TP53, NKX2-5, STAT5A, SP3, TFAP4, POU6F2, NR5A1
Drug & pharmacology data
NF1 is a validated drug target — not through direct protein inhibition, but as the genetic basis for RAS pathway hyperactivation. Loss-of-function NF1 mutations lead to increased RAS/RAF/MEK/ERK signaling; therapeutic strategy targets this dysregulated pathway via downstream kinase inhibitors.
Targeting molecules
Total count: 93 molecules in clinical trials for neurofibromatosis type 1 (MONDO:0018975)
Top molecules by development phase:
| Phase | Molecule | ChEMBL ID | Mechanism | Trials |
|---|---|---|---|---|
| 4 | SELUMETINIB | CHEMBL1614701 | MEK1/2 inhibitor | 110+ |
| 4 | TRAMETINIB | CHEMBL2103875 | MEK1/2 inhibitor | 235+ |
| 4 | DABRAFENIB | CHEMBL2028663 | BRAF inhibitor | 137+ |
| 4 | IMATINIB | CHEMBL941 | TKI (multiple targets) | — |
| 4 | BEVACIZUMAB | CHEMBL1201583 | Anti-VEGF antibody | — |
| 4 | CARBOPLATIN | CHEMBL1351 | Chemotherapy | — |
| 4 | VINCRISTINE | CHEMBL90555 | Microtubule inhibitor | — |
| 3 | TIPIFARNIB | CHEMBL289228 | Farnesyltransferase inhibitor | — |
| 3 | TUNLAMETINIB | CHEMBL5095241 | MEK inhibitor | — |
| 2 | MIRDAMETINIB | CHEMBL507361 | MEK1/2 inhibitor | 23 |
| 2 | CEDIRANIB | CHEMBL2103798 | VEGFR inhibitor | — |
Note: Selumetinib (AZD-6244) received FDA approval specifically for NF1-associated plexiform neurofibromas (2020). Combination dabrafenib+trametinib explored for NF1-MPNST.
Clinical trials
93 total interventions linked to MONDO:0018975. Representative trials:
- Selumetinib monotherapy — Phase 2/3 for plexiform neurofibromas (pediatric/adult); completed trials showed 71% volumetric response
- Dabrafenib + Trametinib — Phase 2 for NF1-associated malignant peripheral nerve sheath tumors (MPNST)
- Mirdametinib — Phase 2 for NF1 optic pathway gliomas
- Supportive: chemotherapy combinations (vincristine/carboplatin), radiation, surgery adjuncts
Pharmacogenomics
NF1 mutation status is the pharmacogenomic determinant:
- NF1-mutant patients show enhanced sensitivity to MEK inhibitors; these drugs are indicated specifically for plexiform neurofibroma burden reduction in NF1 carriers
- Dosing/response: Selumetinib 25 mg twice daily (pediatric); response correlates with tumor NF1 mutational status (germline in constitutional NF1, somatic in tumors)
- No genotype-guided dosing guidelines published, but baseline/on-treatment tumor genomics (NF1 sequencing) inform treatment selection for MPNST vs. optic glioma vs. cutaneous manifestations
- Resistance mechanisms: Emerging secondary RAS pathway mutations (KRAS, HRAS) during MEK inhibitor therapy; combination strategies (MEK + downstream targets) under investigation
Expression profiles
Tissue expression (Bgee)
NF1 exhibits ubiquitous expression across human tissues with strong, consistent expression across 291 documented conditions (283 present, 8 absent).
| Tissue | Expression Score | Quality |
|---|---|---|
| Colonic epithelium | 94.30 | Gold |
| Calcaneal tendon | 94.26 | Gold |
| Adrenal tissue | 93.29 | Gold |
| Secondary oocyte | 92.75 | Gold |
| Ventricular zone | 92.40 | Gold |
| Oocyte | 91.92 | Gold |
| Buccal mucosa cell | 91.87 | Gold |
| Sural nerve | 91.78 | Gold |
| Ganglionic eminence | 91.68 | Gold |
| Male germ line stem cell (testis) | 91.32 | Gold |
| Tendon | 91.26 | Gold |
| Corpus callosum | 91.13 | Gold |
| Cortical plate | 89.89 | Gold |
| Corpus epididymis | 89.58 | Gold |
| CA1 field of hippocampus | 89.30 | Gold |
| Stromal cell of endometrium | 89.17 | Gold |
| Postcentral gyrus | 89.14 | Gold |
| Tonsil | 89.04 | Gold |
| Cauda epididymis | 88.96 | Gold |
| Embryo | 88.95 | Gold |
| Cerebellar hemisphere | 88.83 | Gold |
| Choroid plexus epithelium | 88.82 | Gold |
| Cerebellar cortex | 88.80 | Gold |
| Caput epididymis | 88.77 | Gold |
| Left testis | 88.65 | Gold |
| Brodmann area 46 | 88.40 | Gold |
| Testis | 88.37 | Gold |
| Right testis | 88.35 | Gold |
| Orbitofrontal cortex | 88.31 | Gold |
| Heart right ventricle | 88.29 | Gold |
Mean expression score: 82.94 across all tissues. Notable patterns: High expression in epithelial tissues (colonic epithelium, buccal mucosa), connective tissues (tendons), reproductive tissues (oocytes, testis, epididymis), and nervous system structures (ventricular zone, hippocampus, cerebellar regions).
Cell-type expression (Single-cell RNA-seq, GTEx atlas)
NF1 is detected across 78+ cell types from the GTEx single-nucleus RNA-seq atlas (E-ANND-2, 209,126 cells) spanning multiple tissues:
| Cell Type | Notable Expression Contexts |
|---|---|
| Epithelial cells (basal, luminal, ciliated) | Extensive, multiple subtypes |
| Schwann cells | High (I & II) – peripheral nerve cells |
| Fibroblasts | Multiple subtypes (I, II, III) |
| Myocytes | Skeletal, cardiac, smooth muscle |
| Immune cells | Macrophages, T cells, B cells, NK cells, dendritic cells |
| Endothelial cells | Vascular, lymphatic, cardiac microvascular |
| Pericytes/SMC | Vascular support cells |
| Myofibroblasts | Fibroblast-myocyte hybrids |
| Adipocytes | Lipid-laden cells |
| Neuroendocrine cells | Hormone-secreting cells |
| Melanocytes | Pigment cells |
Tissues represented: Breast, lung, skin, heart, skeletal muscle, esophagus, prostate. NF1 marker score in GTEx: ~19.0 (moderate, widely distributed marker gene, consistent with ubiquitous expression pattern).
Single-cell datasets of interest
- E-ANND-2 (GTEx snRNAseq atlas) – 209,126 cells across 19 tissue types; highest resolution publicly available single-nucleus map of human tissues.
- E-GEOD-75688 – Primary breast cancer cells and lymph node metastases (549 cells); relevant for understanding NF1 in cancer contexts given NF1’s role in neurofibromatosis type 1.
Disease associations
Mendelian / Monogenic Diseases
Primary NF1-Related Conditions:
| Disease | Disease ID | Inheritance | Evidence Level |
|---|---|---|---|
| Neurofibromatosis type 1 | OMIM:162200 | Autosomal dominant | Definitive |
| Neurofibromatosis-Noonan syndrome | OMIM:601321 | Autosomal dominant | Strong |
| Mosaic neurofibromatosis type 1 | MONDO:0859763 | Somatic/Mosaic | Supportive |
| NF1 due to NF1 mutation or intragenic deletion | MONDO:0018208 | Autosomal dominant | Definitive |
Associated Disorders (GenCC-curated):
- Hereditary pheochromocytoma-paraganglioma (ORPHANET:29072) - Supportive/Autosomal dominant
- Familial ovarian cancer (MONDO:0016248) - No Known Disease Relationship
- Moyamoya disease (MONDO:0016820) - Moderate/Autosomal dominant
Secondary Neoplasias & Related Conditions (ClinVar-linked, n=51):
- Juvenile myelomonocytic leukemia (MONDO:0011908; ORPHANET:86834)
- Optic nerve glioma (MONDO:0003235)
- Rhabdomyosarcoma (MONDO:0005212)
- Pheochromocytoma (MONDO:0008233)
- Gastric cancer (MONDO:0001056)
- Breast-ovarian cancer, familial (MONDO:0003582; MONDO:0011450)
- Ewing sarcoma (MONDO:0012817)
- Retinoblastoma (MONDO:0008380)
- Diffuse large B-cell lymphoma (MONDO:0018905)
- Diffuse intrinsic pontine glioma (MONDO:0006033)
- Brainstem gliomas
- Craniopharyngioma (ORPHANET:54595)
- Plexiform neurofibroma (MONDO:0003304; ORPHANET:252183)
- Urinary bladder cancer (MONDO:0001187)
- Ovarian cancer (MONDO:0008170)
Developmental & Syndromic Features:
- 17q11.2 microduplication syndrome (ORPHANET:139474)
- 17q11.2 microdeletion syndrome (ORPHANET:97685)
- RASopathy (MONDO:0021060; ORPHANET:536391)
- Intellectual disability (MONDO:0001071)
- Autism spectrum disorder (MONDO:0005258)
- Keratoconus (MONDO:0015486)
Phenotype Associations (HPO Terms - Top 30 Most Clinically Relevant)
| Phenotype | HPO ID | Category |
|---|---|---|
| Café-au-lait spots, multiple | HP:0007565 | Dermatologic (hallmark) |
| Neurofibroma | HP:0001067 | Neoplastic (hallmark) |
| Plexiform neurofibroma | HP:0009732 | Neoplastic |
| Freckling | HP:0001480 | Dermatologic |
| Axillary freckling | HP:0000997 | Dermatologic |
| Lisch nodules | HP:0009737 | Ocular (hallmark) |
| Optic nerve glioma | HP:0009734 | Neoplastic |
| Pheochromocytoma | HP:0002666 | Neoplastic |
| Paraganglioma | HP:0002668 | Neoplastic |
| Intellectual disability | HP:0001249 | Neurologic |
| Global developmental delay | HP:0001263 | Neurologic |
| Seizure | HP:0001250 | Neurologic |
| Speech and language development delay | HP:0000750 | Neurologic |
| Attention deficit hyperactivity disorder | HP:0007018 | Behavioral |
| Autistic behavior | HP:0000729 | Behavioral |
| Macrocephaly | HP:0000256 | Craniofacial |
| Short stature | HP:0004322 | Systemic |
| Scoliosis | HP:0002650 | Skeletal |
| Tibial pseudarthrosis | HP:0009736 | Skeletal |
| Kyphoscoliosis | HP:0002751 | Skeletal |
| Hypertension | HP:0000822 | Cardiovascular |
| Pectus excavatum | HP:0000767 | Skeletal |
| Strabismus | HP:0000486 | Ocular |
| Renal artery stenosis | HP:0001920 | Vascular |
| Coarctation of aorta | HP:0001680 | Cardiovascular |
| Dural ectasia | HP:0100775 | Skeletal/CNS |
| Headache | HP:0002315 | Neurologic |
| Learning disability | HP:0001328 | Neurologic |
| Polyneuro pathy | HP:0001271 | Neurologic |
| Hypermelanotic macule | HP:0001034 | Dermatologic |
Complex-Disease / GWAS Associations (Top 30)
Metabolic Traits (Strongest Associations):
| Trait | P-value | Study ID | Details |
|---|---|---|---|
| Appendicular lean mass | 2e-25 | GCST90000025 | NF1-RAB11FIP4 locus |
| Platelet count | 1e-19 | GCST90002402 | Hematologic |
| Monocyte count | 9e-19 | GCST90002393 | Hematologic |
| Adventurousness (personality) | 6e-19 | GCST007324 | Behavioral |
| Apolipoprotein B levels | 1e-17 | GCST010243 | Lipid metabolism |
| Total cholesterol | 7e-14 | GCST009145 | Lipid metabolism |
| LDL cholesterol levels | 1e-14 | GCST010245 | Lipid metabolism |
| Aspartate aminotransferase levels | 1e-13 | GCST90011899 | Liver function (NF1, EVI2B) |
| Hip circumference (BMI-adjusted) | 3e-15 | GCST012227 | Anthropometric |
| Low density lipoprotein | 3e-14 | GCST010204 | Lipid metabolism |
Cancer & Disease Susceptibility:
| Trait | P-value | Study ID |
|---|---|---|
| Endometrial cancer | 4e-08 | GCST006464 |
| Endometrial cancer (endometrioid) | 1e-07 | GCST006465 |
| Familial squamous cell lung carcinoma | 1e-06 | GCST006088 |
Behavioral, Metabolic & Anthropometric:
| Trait | P-value | Study ID |
|---|---|---|
| General risk tolerance (MTAG) | 2e-19 | GCST007325 |
| Feeling nervous | 3e-08 | GCST006948 |
| Monocyte percentage of WBC | 9e-12 | GCST90002394 |
| Plateletcrit | 4e-12 | GCST90002400 |
| Body size at age 10 | 2e-08 | GCST010989 |
| Hip circumference | 2e-08 | GCST004066 |
| Hip circumference (BMI-adjusted) | 2e-07 | GCST008156 |
| Hemorrhoidal disease | 7e-10 | GCST90014033 |
| Bitter alcoholic beverage consumption | 2e-07 | GCST008522 |
| Oily fish consumption | 3e-10 | GCST010135 |
| Pork consumption | 3e-10 | GCST010140 |
| Type 2 diabetes | 4e-11 | GCST010118 |
| Brain morphology (MOSTest) | 4e-10 | GCST010703 |